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395 results on '"Abrignani S"'

1. Evidence for a pathogenic role of extrafollicular, IL-10–producing CCR6⁺B helper T cells in systemic lupus erythematosus

Author

Facciotti, F., Larghi, P., Bosotti, R., Vasco, C., Gagliani, N., Cordiglierif, C., Mazzarag, S., Ranzani, V., Rottoli, E., Curti, S., Penatti, A., Karnani, B., Kobayashi, Y., Crosti, M., Bombaci, M., van Hamburg, J. P., Rossetti, G., Gualtierotti, R., Gerosa, M., Gatti, S., Torretta, S., Pignataro, L., Tas, S. W., Abrignani, S., Pagani, M., Grassi, F., Meroni, P. L., Flavell, R. A., and Geginat, J.

Published
2020

3. Corrigendum: The Impact of Anti-rheumatic Drugs on the Seroprevalence of Anti-SARS-CoV-2 Antibodies in a Cohort of Patients With Inflammatory Arthritis: The MAINSTREAM Study(Front. Med., (2022), 9, (850858), 10.3389/fmed.2022.850858)

Author

Favalli E. G., Favalli, E, Gobbini, A, Bombaci, M, Maioli, G, Biggioggero, M, Pesce, E, Favalli, A, Martinovic, M, Fabbris, T, Marchisio, E, Bandera, A, Gori, A, Abrignani, S, Grifantini, R, Caporali, R, Favalli E. G., Gobbini A., Bombaci M., Maioli G., Biggioggero M., Pesce E., Favalli A., Martinovic M., Fabbris T., Marchisio E., Bandera A., Gori A., Abrignani S., Grifantini R., Caporali R., Favalli E. G., Favalli, E, Gobbini, A, Bombaci, M, Maioli, G, Biggioggero, M, Pesce, E, Favalli, A, Martinovic, M, Fabbris, T, Marchisio, E, Bandera, A, Gori, A, Abrignani, S, Grifantini, R, Caporali, R, Favalli E. G., Gobbini A., Bombaci M., Maioli G., Biggioggero M., Pesce E., Favalli A., Martinovic M., Fabbris T., Marchisio E., Bandera A., Gori A., Abrignani S., Grifantini R., and Caporali R.

Abstract

[This corrects the article DOI: 10.3389/fmed.2022.850858.]

Published
2022

4. Maturation signatures of conventional dendritic cell subtypes in COVID-19 suggest direct viral sensing

Author

Marongiu, L, Protti, G, Facchini, F, Valache, M, Mingozzi, F, Ranzani, V, Putignano, A, Salviati, L, Bevilacqua, V, Curti, S, Crosti, M, Sarnicola, M, D'Angio, M, Bettini, L, Biondi, A, Nespoli, L, Tamini, N, Clementi, N, Mancini, N, Abrignani, S, Spreafico, R, Granucci, F, Marongiu L., Protti G., Facchini F. A., Valache M., Mingozzi F., Ranzani V., Putignano A. R., Salviati L., Bevilacqua V., Curti S., Crosti M., Sarnicola M. L., D'Angio M., Bettini L. R., Biondi A., Nespoli L., Tamini N., Clementi N., Mancini N., Abrignani S., Spreafico R., Granucci F., Marongiu, L, Protti, G, Facchini, F, Valache, M, Mingozzi, F, Ranzani, V, Putignano, A, Salviati, L, Bevilacqua, V, Curti, S, Crosti, M, Sarnicola, M, D'Angio, M, Bettini, L, Biondi, A, Nespoli, L, Tamini, N, Clementi, N, Mancini, N, Abrignani, S, Spreafico, R, Granucci, F, Marongiu L., Protti G., Facchini F. A., Valache M., Mingozzi F., Ranzani V., Putignano A. R., Salviati L., Bevilacqua V., Curti S., Crosti M., Sarnicola M. L., D'Angio M., Bettini L. R., Biondi A., Nespoli L., Tamini N., Clementi N., Mancini N., Abrignani S., Spreafico R., and Granucci F.

Abstract

Growing evidence suggests that conventional dendritic cells (cDCs) undergo aberrant maturation in COVID-19, which negatively affects T-cell activation. The presence of effector T cells in patients with mild disease and dysfunctional T cells in severely ill patients suggests that adequate T-cell responses limit disease severity. Understanding how cDCs cope with SARS-CoV-2 can help elucidate how protective immune responses are generated. Here, we report that cDC2 subtypes exhibit similar infection-induced gene signatures, with the upregulation of IFN-stimulated genes and IL-6 signaling pathways. Furthermore, comparison of cDCs between patients with severe and mild disease showed severely ill patients to exhibit profound downregulation of genes encoding molecules involved in antigen presentation, such as MHCII, TAP, and costimulatory proteins, whereas we observed the opposite for proinflammatory molecules, such as complement and coagulation factors. Thus, as disease severity increases, cDC2s exhibit enhanced inflammatory properties and lose antigen presentation capacity. Moreover, DC3s showed upregulation of anti-apoptotic genes and accumulated during infection. Direct exposure of cDC2s to the virus in vitro recapitulated the activation profile observed in vivo. Our findings suggest that SARS-CoV-2 interacts directly with cDC2s and implements an efficient immune escape mechanism that correlates with disease severity by downregulating crucial molecules required for T-cell activation.

Published
2022

6. Flow diversion for indirect carotid-cavernous fistula: Still an off-label indication?

Author

Brunasso, L, Casamassima, N, Abrignani, S, Sturiale, CL, Incandela, F, Giammalva, GR, Iacopino, D, Maugeri, R, Craparo, G, Brunasso, L, Casamassima, N, Abrignani, S, Sturiale, CL, Incandela, F, Giammalva, GR, Iacopino, D, Maugeri, R, and Craparo, G

Subjects
Carotid cavernous fistula, Flow diversion, Endovascular treatment, Surgery, Neurology (clinical), Indirect carotid cavernous fistula (Indirect CCF), Barrow B type fistula
Abstract

Background: Flow diversion (FD) is an established treatment for large or giant wide-necked unruptured intracranial aneurysms. In the past few years, the use of flow diverter devices was extended to several other “off-label” indications, including solitary or adjunctive treatment to coil embolization for direct (Barrow A type) carotid cavernous fistulas (CCFs). The use of liquid embolic agents still represents the first-line treatment for indirect CCFs. Typically, the ipsilateral inferior petrosal sinus or superior ophthalmic vein (SOV) is the preferred transvenous routes to access CCFs. In some cases, vessel tortuosity or different features make the endovascular access challenging, thus requiring different approaches and strategies. The aim of the study is to discuss rational and technical aspect in treating indirect CCFs referring to the most up-to-date literature. An alternative experience-based endovascular strategy with FD is described. Methods: We report the case of a 54-year-old woman diagnosed with indirect CCF and treated with flow diverter stent. Results: After multiple unsuccessful attempts at transarterial right SOV catheterization, a right indirect CCF fed by a single trunk at the ophthalmic origin from the internal carotid artery (ICA) was treated by ICA stand-alone FD. Blood flow was redirect and successfully reduced through the fistula, with immediately postprocedure improvement of the patient’s clinical status (ipsilateral proptosis and chemosis). Ten-months radiological follow-up showed the complete obliteration of the fistula. No adjunctive endovascular treatment was performed. Conclusion: FD appears a reasonable alternative stand-alone endovascular strategy also for selected difficult-to-access indirect CCFs, when all conventional routes are judged unfeasible. Further investigations will be necessary to better define and support this potential lesson-learned application.

Published
2023
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7. Integrated longitudinal immunophenotypic, transcriptional and repertoire analyses delineate immune responses in COVID-19 patients

Author

Notarbartolo, S, Ranzani, V, Bandera, A, Gruarin, P, Bevilacqua, V, Putignano, A, Gobbini, A, Galeota, E, Manara, C, Bombaci, M, Pesce, E, Zagato, E, Favalli, A, Sarnicola, M, Curti, S, Crosti, M, Martinovic, M, Fabbris, T, Marini, F, Donnici, L, Lorenzo, M, Mancino, M, Ungaro, R, Lombardi, A, Mangioni, D, Muscatello, A, Aliberti, S, Blasi, F, De Feo, T, Prati, D, Manganaro, L, Granucci, F, Lanzavecchia, A, De Francesco, R, Gori, A, Grifantini, R, Abrignani, S, Notarbartolo S., Ranzani V., Bandera A., Gruarin P., Bevilacqua V., Putignano A. R., Gobbini A., Galeota E., Manara C., Bombaci M., Pesce E., Zagato E., Favalli A., Sarnicola M. L., Curti S., Crosti M., Martinovic M., Fabbris T., Marini F., Donnici L., Lorenzo M., Mancino M., Ungaro R., Lombardi A., Mangioni D., Muscatello A., Aliberti S., Blasi F., De Feo T., Prati D., Manganaro L., Granucci F., Lanzavecchia A., De Francesco R., Gori A., Grifantini R., Abrignani S., Notarbartolo, S, Ranzani, V, Bandera, A, Gruarin, P, Bevilacqua, V, Putignano, A, Gobbini, A, Galeota, E, Manara, C, Bombaci, M, Pesce, E, Zagato, E, Favalli, A, Sarnicola, M, Curti, S, Crosti, M, Martinovic, M, Fabbris, T, Marini, F, Donnici, L, Lorenzo, M, Mancino, M, Ungaro, R, Lombardi, A, Mangioni, D, Muscatello, A, Aliberti, S, Blasi, F, De Feo, T, Prati, D, Manganaro, L, Granucci, F, Lanzavecchia, A, De Francesco, R, Gori, A, Grifantini, R, Abrignani, S, Notarbartolo S., Ranzani V., Bandera A., Gruarin P., Bevilacqua V., Putignano A. R., Gobbini A., Galeota E., Manara C., Bombaci M., Pesce E., Zagato E., Favalli A., Sarnicola M. L., Curti S., Crosti M., Martinovic M., Fabbris T., Marini F., Donnici L., Lorenzo M., Mancino M., Ungaro R., Lombardi A., Mangioni D., Muscatello A., Aliberti S., Blasi F., De Feo T., Prati D., Manganaro L., Granucci F., Lanzavecchia A., De Francesco R., Gori A., Grifantini R., and Abrignani S.

Abstract

To understand how a protective immune response against SARS-CoV-2 develops over time, we integrated phenotypic, transcriptional and repertoire analyses on PBMCs from mild and severe COVID-19 patients during and after infection, and compared them to healthy donors (HD). A type I IFN-response signature marked all the immune populations from severe patients during the infection. Humoral immunity was dominated by IgG production primarily against the RBD and N proteins, with neutralizing antibody titers increasing post infection and with disease severity. Memory B cells, including an atypical FCRL5+ T-BET+ memory subset, increased during the infection, especially in patients with mild disease. A significant reduction of effector memory, CD8+T cells frequency characterized patients with severe disease. Despite such impairment, we observed robust clonal expansion of CD8+T lymphocytes, while CD4+T cells were less expanded and skewed toward TCMand TH2-like phenotypes. MAIT cells were also expanded, but only in patients with mild disease. Terminally differentiated CD8+GZMB+effector cells were clonally expanded both during the infection and post-infection, while CD8+GZMK+lymphocytes were more expanded post-infection and represented bona fide memory precursor effector cells. TCR repertoire analysis revealed that only highly proliferating T cell clonotypes, which included SARS-CoV-2-specific cells, were maintained post-infection and shared between the CD8+GZMB+and GZMK+subsets. Overall, this study describes the development of immunity against SARS-CoV-2 and identifies an effector CD8+T cell population with memory precursor-like features.

Published
2021

8. Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

Author

Cossarizza, A, Chang, H, Radbruch, A, Abrignani, S, Addo, R, Akdis, M, Andra, I, Andreata, F, Annunziato, F, Arranz, E, Bacher, P, Bari, S, Barnaba, V, Barros-Martins, J, Baumjohann, D, Beccaria, C, Bernardo, D, Boardman, D, Borger, J, Bottcher, C, Brockmann, L, Burns, M, Busch, D, Cameron, G, Cammarata, I, Cassotta, A, Chang, Y, Chirdo, F, Christakou, E, Cicin-Sain, L, Cook, L, Corbett, A, Cornelis, R, Cosmi, L, Davey, M, De Biasi, S, De Simone, G, del Zotto, G, Delacher, M, Di Rosa, F, Santo, J, Diefenbach, A, Dong, J, Dorner, T, Dress, R, Dutertre, C, Eckle, S, Eede, P, Evrard, M, Falk, C, Feuerer, M, Fillatreau, S, Fiz-Lopez, A, Follo, M, Foulds, G, Frobel, J, Gagliani, N, Galletti, G, Gangaev, A, Garbi, N, Garrote, J, Geginat, J, Gherardin, N, Gibellini, L, Ginhoux, F, Godfrey, D, Gruarin, P, Haftmann, C, Hansmann, L, Harpur, C, Hayday, A, Heine, G, Hernandez, D, Herrmann, M, Hoelsken, O, Huang, Q, Huber, S, Huber, J, Huehn, J, Hundemer, M, Hwang, W, Iannacone, M, Ivison, S, Jack, H, Jani, P, Keller, B, Kessler, N, Ketelaars, S, Knop, L, Knopf, J, Koay, H, Kobow, K, Kriegsmann, K, Kristyanto, H, Krueger, A, Kuehne, J, Kunze-Schumacher, H, Kvistborg, P, Kwok, I, Latorre, D, Lenz, D, Levings, M, Lino, A, Liotta, F, Long, H, Lugli, E, Macdonald, K, Maggi, L, Maini, M, Mair, F, Manta, C, Manz, R, Mashreghi, M, Mazzoni, A, Mccluskey, J, Mei, H, Melchers, F, Melzer, S, Mielenz, D, Monin, L, Moretta, L, Multhoff, G, Munoz, L, Munoz-Ruiz, M, Muscate, F, Natalini, A, Neumann, K, Ng, L, Niedobitek, A, Niemz, J, Almeida, L, Notarbartolo, S, Ostendorf, L, Pallett, L, Patel, A, Percin, G, Peruzzi, G, Pinti, M, Pockley, A, Pracht, K, Prinz, I, Pujol-Autonell, I, Pulvirenti, N, Quatrini, L, Quinn, K, Radbruch, H, Rhys, H, Rodrigo, M, Romagnani, C, Saggau, C, Sakaguchi, S, Sallusto, F, Sanderink, L, Sandrock, I, Schauer, C, Scheffold, A, Scherer, H, Schiemann, M, Schildberg, F, Schober, K, Schoen, J, Schuh, W, Schuler, T, Schulz, A, Schulz, S, Schulze, J, Simonetti, S, Singh, J, Sitnik, K, Stark, R, Starossom, S, Stehle, C, Szelinski, F, Tan, L, Tarnok, A, Tornack, J, Tree, T, van Beek, J, van de Veen, W, van Gisbergen, K, Vasco, C, Verheyden, N, von Borstel, A, Ward-Hartstonge, K, Warnatz, K, Waskow, C, Wiedemann, A, Wilharm, A, Wing, J, Wirz, O, Wittner, J, Yang, J, Cossarizza A., Chang H. -D., Radbruch A., Abrignani S., Addo R., Akdis M., Andra I., Andreata F., Annunziato F., Arranz E., Bacher P., Bari S., Barnaba V., Barros-Martins J., Baumjohann D., Beccaria C. G., Bernardo D., Boardman D. A., Borger J., Bottcher C., Brockmann L., Burns M., Busch D. H., Cameron G., Cammarata I., Cassotta A., Chang Y., Chirdo F. G., Christakou E., Cicin-Sain L., Cook L., Corbett A. J., Cornelis R., Cosmi L., Davey M. S., De Biasi S., De Simone G., del Zotto G., Delacher M., Di Rosa F., Santo J. D., Diefenbach A., Dong J., Dorner T., Dress R. J., Dutertre C. -A., Eckle S. B. G., Eede P., Evrard M., Falk C. S., Feuerer M., Fillatreau S., Fiz-Lopez A., Follo M., Foulds G. A., Frobel J., Gagliani N., Galletti G., Gangaev A., Garbi N., Garrote J. A., Geginat J., Gherardin N. A., Gibellini L., Ginhoux F., Godfrey D. I., Gruarin P., Haftmann C., Hansmann L., Harpur C. M., Hayday A. C., Heine G., Hernandez D. C., Herrmann M., Hoelsken O., Huang Q., Huber S., Huber J. E., Huehn J., Hundemer M., Hwang W. Y. K., Iannacone M., Ivison S. M., Jack H. -M., Jani P. K., Keller B., Kessler N., Ketelaars S., Knop L., Knopf J., Koay H. -F., Kobow K., Kriegsmann K., Kristyanto H., Krueger A., Kuehne J. F., Kunze-Schumacher H., Kvistborg P., Kwok I., Latorre D., Lenz D., Levings M. K., Lino A. C., Liotta F., Long H. M., Lugli E., MacDonald K. N., Maggi L., Maini M. K., Mair F., Manta C., Manz R. A., Mashreghi M. -F., Mazzoni A., McCluskey J., Mei H. E., Melchers F., Melzer S., Mielenz D., Monin L., Moretta L., Multhoff G., Munoz L. E., Munoz-Ruiz M., Muscate F., Natalini A., Neumann K., Ng L. G., Niedobitek A., Niemz J., Almeida L. N., Notarbartolo S., Ostendorf L., Pallett L. J., Patel A. A., Percin G. I., Peruzzi G., Pinti M., Pockley A. G., Pracht K., Prinz I., Pujol-Autonell I., Pulvirenti N., Quatrini L., Quinn K. M., Radbruch H., Rhys H., Rodrigo M. B., Romagnani C., Saggau C., Sakaguchi S., Sallusto F., Sanderink L., Sandrock I., Schauer C., Scheffold A., Scherer H. U., Schiemann M., Schildberg F. A., Schober K., Schoen J., Schuh W., Schuler T., Schulz A. R., Schulz S., Schulze J., Simonetti S., Singh J., Sitnik K. M., Stark R., Starossom S., Stehle C., Szelinski F., Tan L., Tarnok A., Tornack J., Tree T. I. M., van Beek J. J. P., van de Veen W., van Gisbergen K., Vasco C., Verheyden N. A., von Borstel A., Ward-Hartstonge K. A., Warnatz K., Waskow C., Wiedemann A., Wilharm A., Wing J., Wirz O., Wittner J., Yang J. H. M., Yang J., Cossarizza, A, Chang, H, Radbruch, A, Abrignani, S, Addo, R, Akdis, M, Andra, I, Andreata, F, Annunziato, F, Arranz, E, Bacher, P, Bari, S, Barnaba, V, Barros-Martins, J, Baumjohann, D, Beccaria, C, Bernardo, D, Boardman, D, Borger, J, Bottcher, C, Brockmann, L, Burns, M, Busch, D, Cameron, G, Cammarata, I, Cassotta, A, Chang, Y, Chirdo, F, Christakou, E, Cicin-Sain, L, Cook, L, Corbett, A, Cornelis, R, Cosmi, L, Davey, M, De Biasi, S, De Simone, G, del Zotto, G, Delacher, M, Di Rosa, F, Santo, J, Diefenbach, A, Dong, J, Dorner, T, Dress, R, Dutertre, C, Eckle, S, Eede, P, Evrard, M, Falk, C, Feuerer, M, Fillatreau, S, Fiz-Lopez, A, Follo, M, Foulds, G, Frobel, J, Gagliani, N, Galletti, G, Gangaev, A, Garbi, N, Garrote, J, Geginat, J, Gherardin, N, Gibellini, L, Ginhoux, F, Godfrey, D, Gruarin, P, Haftmann, C, Hansmann, L, Harpur, C, Hayday, A, Heine, G, Hernandez, D, Herrmann, M, Hoelsken, O, Huang, Q, Huber, S, Huber, J, Huehn, J, Hundemer, M, Hwang, W, Iannacone, M, Ivison, S, Jack, H, Jani, P, Keller, B, Kessler, N, Ketelaars, S, Knop, L, Knopf, J, Koay, H, Kobow, K, Kriegsmann, K, Kristyanto, H, Krueger, A, Kuehne, J, Kunze-Schumacher, H, Kvistborg, P, Kwok, I, Latorre, D, Lenz, D, Levings, M, Lino, A, Liotta, F, Long, H, Lugli, E, Macdonald, K, Maggi, L, Maini, M, Mair, F, Manta, C, Manz, R, Mashreghi, M, Mazzoni, A, Mccluskey, J, Mei, H, Melchers, F, Melzer, S, Mielenz, D, Monin, L, Moretta, L, Multhoff, G, Munoz, L, Munoz-Ruiz, M, Muscate, F, Natalini, A, Neumann, K, Ng, L, Niedobitek, A, Niemz, J, Almeida, L, Notarbartolo, S, Ostendorf, L, Pallett, L, Patel, A, Percin, G, Peruzzi, G, Pinti, M, Pockley, A, Pracht, K, Prinz, I, Pujol-Autonell, I, Pulvirenti, N, Quatrini, L, Quinn, K, Radbruch, H, Rhys, H, Rodrigo, M, Romagnani, C, Saggau, C, Sakaguchi, S, Sallusto, F, Sanderink, L, Sandrock, I, Schauer, C, Scheffold, A, Scherer, H, Schiemann, M, Schildberg, F, Schober, K, Schoen, J, Schuh, W, Schuler, T, Schulz, A, Schulz, S, Schulze, J, Simonetti, S, Singh, J, Sitnik, K, Stark, R, Starossom, S, Stehle, C, Szelinski, F, Tan, L, Tarnok, A, Tornack, J, Tree, T, van Beek, J, van de Veen, W, van Gisbergen, K, Vasco, C, Verheyden, N, von Borstel, A, Ward-Hartstonge, K, Warnatz, K, Waskow, C, Wiedemann, A, Wilharm, A, Wing, J, Wirz, O, Wittner, J, Yang, J, Cossarizza A., Chang H. -D., Radbruch A., Abrignani S., Addo R., Akdis M., Andra I., Andreata F., Annunziato F., Arranz E., Bacher P., Bari S., Barnaba V., Barros-Martins J., Baumjohann D., Beccaria C. G., Bernardo D., Boardman D. A., Borger J., Bottcher C., Brockmann L., Burns M., Busch D. H., Cameron G., Cammarata I., Cassotta A., Chang Y., Chirdo F. G., Christakou E., Cicin-Sain L., Cook L., Corbett A. J., Cornelis R., Cosmi L., Davey M. S., De Biasi S., De Simone G., del Zotto G., Delacher M., Di Rosa F., Santo J. D., Diefenbach A., Dong J., Dorner T., Dress R. J., Dutertre C. -A., Eckle S. B. G., Eede P., Evrard M., Falk C. S., Feuerer M., Fillatreau S., Fiz-Lopez A., Follo M., Foulds G. A., Frobel J., Gagliani N., Galletti G., Gangaev A., Garbi N., Garrote J. A., Geginat J., Gherardin N. A., Gibellini L., Ginhoux F., Godfrey D. I., Gruarin P., Haftmann C., Hansmann L., Harpur C. M., Hayday A. C., Heine G., Hernandez D. C., Herrmann M., Hoelsken O., Huang Q., Huber S., Huber J. E., Huehn J., Hundemer M., Hwang W. Y. K., Iannacone M., Ivison S. M., Jack H. -M., Jani P. K., Keller B., Kessler N., Ketelaars S., Knop L., Knopf J., Koay H. -F., Kobow K., Kriegsmann K., Kristyanto H., Krueger A., Kuehne J. F., Kunze-Schumacher H., Kvistborg P., Kwok I., Latorre D., Lenz D., Levings M. K., Lino A. C., Liotta F., Long H. M., Lugli E., MacDonald K. N., Maggi L., Maini M. K., Mair F., Manta C., Manz R. A., Mashreghi M. -F., Mazzoni A., McCluskey J., Mei H. E., Melchers F., Melzer S., Mielenz D., Monin L., Moretta L., Multhoff G., Munoz L. E., Munoz-Ruiz M., Muscate F., Natalini A., Neumann K., Ng L. G., Niedobitek A., Niemz J., Almeida L. N., Notarbartolo S., Ostendorf L., Pallett L. J., Patel A. A., Percin G. I., Peruzzi G., Pinti M., Pockley A. G., Pracht K., Prinz I., Pujol-Autonell I., Pulvirenti N., Quatrini L., Quinn K. M., Radbruch H., Rhys H., Rodrigo M. B., Romagnani C., Saggau C., Sakaguchi S., Sallusto F., Sanderink L., Sandrock I., Schauer C., Scheffold A., Scherer H. U., Schiemann M., Schildberg F. A., Schober K., Schoen J., Schuh W., Schuler T., Schulz A. R., Schulz S., Schulze J., Simonetti S., Singh J., Sitnik K. M., Stark R., Starossom S., Stehle C., Szelinski F., Tan L., Tarnok A., Tornack J., Tree T. I. M., van Beek J. J. P., van de Veen W., van Gisbergen K., Vasco C., Verheyden N. A., von Borstel A., Ward-Hartstonge K. A., Warnatz K., Waskow C., Wiedemann A., Wilharm A., Wing J., Wirz O., Wittner J., Yang J. H. M., and Yang J.

Abstract

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers.

Published
2021

9. Ex vivo microRNA and gene expression profiling of human Tr1-like cells suggests a role for miR-92a and -125a in the regulation of EOMES and IL-10R

Author

De Simone, M, Chirichella, M, Emming, S, Mazzara, S, Ranzani, V, Gruarin, P, Moschetti, G, Pulvirenti, N, Maglie, S, Vasco, C, Crosti, M, Rossetti, G, Pagani, M, Abrignani, S, Monticelli, S, Geginat, J, De Simone M., Chirichella M., Emming S., Mazzara S., Ranzani V., Gruarin P., Moschetti G., Pulvirenti N., Maglie S., Vasco C., Crosti M. C., Rossetti G., Pagani M., Abrignani S., Monticelli S., Geginat J., De Simone, M, Chirichella, M, Emming, S, Mazzara, S, Ranzani, V, Gruarin, P, Moschetti, G, Pulvirenti, N, Maglie, S, Vasco, C, Crosti, M, Rossetti, G, Pagani, M, Abrignani, S, Monticelli, S, Geginat, J, De Simone M., Chirichella M., Emming S., Mazzara S., Ranzani V., Gruarin P., Moschetti G., Pulvirenti N., Maglie S., Vasco C., Crosti M. C., Rossetti G., Pagani M., Abrignani S., Monticelli S., and Geginat J.

Abstract

Ex vivo gene expression and miRNA profiling of Eomes+ Tr1-like cells suggested that they represent a differentiation stage that is intermediate between Th1-cells and cytotoxic CD4+ T-cells. Several microRNAs were downregulated in Eomes+ Tr1-like cells that might inhibit Tr1-cell differentiation. In particular, miR-92a targeted Eomes, while miR-125a inhibited IFN-g and IL-10R expression.

Published
2021

10. Evidence for a pathogenic role of extrafollicular, IL-10-producing CCR6+B helper T cells in systemic lupus erythematosus

Author

Facciotti, F, Larghi, P, Bosotti, R, Vasco, C, Gagliani, N, Cordiglieri, C, Mazzara, S, Ranzani, V, Rottoli, E, Curti, S, Penatti, A, Karnani, B, Kobayashi, Y, Crosti, M, Bombaci, M, van Hamburg, J, Rossetti, G, Gualtierotti, R, Gerosa, M, Gatti, S, Torretta, S, Pignataro, L, Tas, S, Abrignani, S, Pagani, M, Grassi, F, Meroni, P, Flavell, R, Geginat, J, Facciotti F, Larghi P, Bosotti R, Vasco C, Gagliani N, Cordiglieri C, Mazzara S, Ranzani V, Rottoli E, Curti S, Penatti A, Karnani B, Kobayashi Y, Crosti M, Bombaci M, van Hamburg JP, Rossetti G, Gualtierotti R, Gerosa M, Gatti S, Torretta S, Pignataro L, Tas SW, Abrignani S, Pagani M, Grassi F, Meroni PL, Flavell RA, Geginat J, Facciotti, F, Larghi, P, Bosotti, R, Vasco, C, Gagliani, N, Cordiglieri, C, Mazzara, S, Ranzani, V, Rottoli, E, Curti, S, Penatti, A, Karnani, B, Kobayashi, Y, Crosti, M, Bombaci, M, van Hamburg, J, Rossetti, G, Gualtierotti, R, Gerosa, M, Gatti, S, Torretta, S, Pignataro, L, Tas, S, Abrignani, S, Pagani, M, Grassi, F, Meroni, P, Flavell, R, Geginat, J, Facciotti F, Larghi P, Bosotti R, Vasco C, Gagliani N, Cordiglieri C, Mazzara S, Ranzani V, Rottoli E, Curti S, Penatti A, Karnani B, Kobayashi Y, Crosti M, Bombaci M, van Hamburg JP, Rossetti G, Gualtierotti R, Gerosa M, Gatti S, Torretta S, Pignataro L, Tas SW, Abrignani S, Pagani M, Grassi F, Meroni PL, Flavell RA, and Geginat J

Abstract

Interleukin 10 (IL-10) is an antiinflammatory cytokine, but also promotes B cell responses and plays a pathogenic role in systemic lupus erythematosus (SLE). CD4+CCR6+IL-7R+T cells from human tonsils produced IL-10 following stimulation by naïve B cells, which promoted B cell immunoglobulin G (IgG) production. These tonsillar CCR6+B helper T cells were phenotypically distinct from follicular helper T (TFH) cells and lacked BCL6 expression. In peripheral blood, a CCR6+T cell population with similar characteristics was identified, which lacked Th17- and TFH-associated gene signatures and differentiation-associated surface markers. CD4+CCR6+T cells expressing IL-10, but not IL-17, were also detectable in the spleens of cytokine reporter mice. They provided help for IgG production in vivo, and expanded systemically in pristane-induced lupus-like disease. In SLE patients, CD4+CCR6+IL-7R+T cells were associated with the presence of pathogenic anti-dsDNA (doublestranded DNA) antibodies, and provided spontaneous help for autoantibody production ex vivo. Strikingly, IL-10-producing CCR6+T cells were highly abundant in lymph nodes of SLE patients, and colocalized with B cells at the margins of follicles. In conclusion, we identified a previously uncharacterized population of extrafollicular B helper T cells, which produced IL-10 and could play a prominent pathogenic role in SLE.

Published
2020

11. LINE1 are spliced in non-canonical transcript variants to regulate T cell quiescence and exhaustion

Author

Marasca, F, Sinha, S, Vadalà, R, Polimeni, B, Ranzani, V, Paraboschi, E, Burattin, F, Ghilotti, M, Crosti, M, Negri, M, Campagnoli, S, Notarbartolo, S, Sartore-Bianchi, A, Siena, S, Prati, D, Montini, G, Viale, G, Torre, O, Harari, S, Grifantini, R, Soldà, G, Biffo, S, Abrignani, S, Bodega, B, Marasca, Federica, Sinha, Shruti, Vadalà, Rebecca, Polimeni, Benedetto, Ranzani, Valeria, Paraboschi, Elvezia Maria, Burattin, Filippo Vittorio, Ghilotti, Marco, Crosti, Mariacristina, Negri, Maria Luce, Campagnoli, Susanna, Notarbartolo, Samuele, Sartore-Bianchi, Andrea, Siena, Salvatore, Prati, Daniele, Montini, Giovanni, Viale, Giuseppe, Torre, Olga, Harari, Sergio, Grifantini, Renata, Soldà, Giulia, Biffo, Stefano, Abrignani, Sergio, Bodega, Beatrice, Marasca, F, Sinha, S, Vadalà, R, Polimeni, B, Ranzani, V, Paraboschi, E, Burattin, F, Ghilotti, M, Crosti, M, Negri, M, Campagnoli, S, Notarbartolo, S, Sartore-Bianchi, A, Siena, S, Prati, D, Montini, G, Viale, G, Torre, O, Harari, S, Grifantini, R, Soldà, G, Biffo, S, Abrignani, S, Bodega, B, Marasca, Federica, Sinha, Shruti, Vadalà, Rebecca, Polimeni, Benedetto, Ranzani, Valeria, Paraboschi, Elvezia Maria, Burattin, Filippo Vittorio, Ghilotti, Marco, Crosti, Mariacristina, Negri, Maria Luce, Campagnoli, Susanna, Notarbartolo, Samuele, Sartore-Bianchi, Andrea, Siena, Salvatore, Prati, Daniele, Montini, Giovanni, Viale, Giuseppe, Torre, Olga, Harari, Sergio, Grifantini, Renata, Soldà, Giulia, Biffo, Stefano, Abrignani, Sergio, and Bodega, Beatrice

Abstract

How gene expression is controlled to preserve human T cell quiescence is poorly understood. Here we show that non-canonical splicing variants containing long interspersed nuclear element 1 (LINE1) enforce naive CD4+ T cell quiescence. LINE1-containing transcripts are derived from CD4+ T cell-specific genes upregulated during T cell activation. In naive CD4+ T cells, LINE1-containing transcripts are regulated by the transcription factor IRF4 and kept at chromatin by nucleolin; these transcripts act in cis, hampering levels of histone 3 (H3) lysine 36 trimethyl (H3K36me3) and stalling gene expression. T cell activation induces LINE1-containing transcript downregulation by the splicing suppressor PTBP1 and promotes expression of the corresponding protein-coding genes by the elongating factor GTF2F1 through mTORC1. Dysfunctional T cells, exhausted in vitro or tumor-infiltrating lymphocytes (TILs), accumulate LINE1-containing transcripts at chromatin. Remarkably, depletion of LINE1-containing transcripts restores TIL effector function. Our study identifies a role for LINE1 elements in maintaining T cell quiescence and suggests that an abundance of LINE1-containing transcripts is critical for T cell effector function and exhaustion.

Published
2022

12. POS0254 IMMUNE RESPONSE TO SARS-CoV-2 INFECTION IN PATIENTS WITH RHEUMATIC MUSCULOSKELETAL DISEASES: THE MAINSTREAM STUDY

Author

Favalli, E. G., primary, Favalli, A., additional, Andrea, G., additional, Maioli, G., additional, Zagato, E., additional, Bombaci, M., additional, Pesce, E., additional, Donnici, L., additional, Gruarin, P., additional, Biggioggero, M., additional, Curti, S., additional, Manganaro, L., additional, Marchisio, E., additional, Bevilacqua, V., additional, Martinovic, M., additional, Fabbris, T., additional, Sarnicola, M. L., additional, Crosti, M., additional, Marongiu, L., additional, Granucci, F., additional, Notabartolo, S., additional, Bandera, A., additional, Gori, A., additional, De Francesco, R., additional, Abrignani, S., additional, Caporali, R., additional, and Grifantini, R., additional

Published
2022
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13. A vision of immuno-oncology: the Siena think tank of the Italian network for tumor biotherapy (NIBIT) foundation

Author

Maio M., Lahn M., Di Giacomo A. M., Covre A., Calabro L., Ibrahim R., Fox B., Abrignani S., Paola A., Anichini A., Ardizzoni A., Gregorio A., Azab M., Ballas M., Barberis M., Bayless N. L., Bell B., Bifarini A., Blank C., Brodin P., Camerini R., Ennio C., Ceccarelli M., Francesca C., Connolly J., Sandra C., Cornelissen R., Eggermont A., Eid J., Fajgenbaum D., Ferretti E., Ferrone S., Finotello F., Flaherty K., Ester F., Elisabetta F., Fridman C. S., Fridman W. H., Garcia P., Gherardini P. F., Goonewardene A., Hacking G., Heller K., Hulett T. W., Michael I., Jacobson D., Janek M., Joho S., Keer H., Kleif S., Kotecha N., Kotter M., Krogan N., Lanzavecchia A., Locatelli F., Lollini P. -L., Mantovani A., Melacarne A., Melillo G., Menden M., Minerva D., Moretta L., Namouni F., Natali P. G., Necchi A., Nistico P., Cosimo P., Giuseppe P., Pardoll D., Paz-Ares L., Plessala K., Peters S., Prins R. M., Provendier O., Rappuoli R., Rescigno M., Ruettinger D., Seliger B., Sette A., Luca S., Spasic M., Tortora G., Trajanoski Z., Tunici P., Vitale C., Wigginton J., Yadav M., Yu H., Maio, Michele, Lahn, Michael, Di Giacomo, Anna Maria, Covre, Alessia, Calabrò, Luana, Ibrahim, Ramy, Fox, Bernard, Siena Think Tank, Lollini, Pier-Luigi, Pulmonary Medicine, Maio, M., Lahn, M., Di Giacomo, A. M., Covre, A., Calabro, L., Ibrahim, R., Fox, B., Abrignani, S., Paola, A., Anichini, A., Ardizzoni, A., Gregorio, A., Azab, M., Ballas, M., Barberis, M., Bayless, N. L., Bell, B., Bifarini, A., Blank, C., Brodin, P., Camerini, R., Ennio, C., Ceccarelli, M., Francesca, C., Connolly, J., Sandra, C., Cornelissen, R., Eggermont, A., Eid, J., Fajgenbaum, D., Ferretti, E., Ferrone, S., Finotello, F., Flaherty, K., Ester, F., Elisabetta, F., Fridman, C. S., Fridman, W. H., Garcia, P., Gherardini, P. F., Goonewardene, A., Hacking, G., Heller, K., Hulett, T. W., Michael, I., Jacobson, D., Janek, M., Joho, S., Keer, H., Kleif, S., Kotecha, N., Kotter, M., Krogan, N., Lanzavecchia, A., Locatelli, F., Lollini, P. -L., Mantovani, A., Melacarne, A., Melillo, G., Menden, M., Minerva, D., Moretta, L., Namouni, F., Natali, P. G., Necchi, A., Nistico, P., Cosimo, P., Giuseppe, P., Pardoll, D., Paz-Ares, L., Plessala, K., Peters, S., Prins, R. M., Provendier, O., Rappuoli, R., Rescigno, M., Ruettinger, D., Seliger, B., Sette, A., Luca, S., Spasic, M., Tortora, G., Trajanoski, Z., Tunici, P., Vitale, C., Wigginton, J., Yadav, M., and Yu, H.

Subjects
0301 basic medicine, Oncology, Mesothelioma, Cancer Research, Artificial intelligence, Research areas, medicine.medical_treatment, Corona virus disease 19 (COVID-19), Glioblastoma, Immunotherapy, Melanoma, Novel treatments, PD-L1, PD1, Antibodies, Monoclonal, COVID-19, Humans, Immunity, Italy, Medical Oncology, Neoplasms, Meeting Report, 0302 clinical medicine, Monoclonal, RC254-282, Foundation (evidence), Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Immunotherapy, Novel treatments, PD1, PD-L1, Melanoma, Mesothelioma, Artificial intelligence, Glioblastoma, Corona virus disease 19 (COVID-19), 030220 oncology & carcinogenesis, Non small cell, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Antibodies, NO, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Novel treatment, Tumor microenvironment, business.industry, Cancer, medicine.disease, 030104 developmental biology, business
Abstract

Background The yearly Think Tank Meeting of the Italian Network for Tumor Biotherapy (NIBIT) Foundation, brings together in Siena, Tuscany (Italy), experts in immuno-oncology to review the learnings from current immunotherapy treatments, and to propose new pre-clinical and clinical investigations in selected research areas. Main While immunotherapies in non-small cell lung cancer and melanoma led to practice changing therapies, the same therapies had only modest benefit for patients with other malignancies, such as mesothelioma and glioblastoma. One way to improve on current immunotherapies is to alter the sequence of each combination agent. Matching the immunotherapy to the host’s immune response may thus improve the activity of the current treatments. A second approach is to combine current immunotherapies with novel agents targeting complementary mechanisms. Identifying the appropriate novel agents may require different approaches than the traditional laboratory-based discovery work. For example, artificial intelligence-based research may help focusing the search for innovative and most promising combination partners. Conclusion Novel immunotherapies are needed in cancer patients with resistance to or relapse after current immunotherapeutic drugs. Such new treatments may include targeted agents or monoclonal antibodies to overcome the immune-suppressive tumor microenvironment. The mode of combining the novel treatments, including vaccines, needs to be matched to the patient’s immune status for achieving the maximum benefit. In this scenario, specific attention should be also paid nowadays to the immune intersection between COVID-19 and cancer.

Published
2021

14. FLOW DIVERTER DEVICE IN THE ACUTE SETTING OF RUPTURED BLISTER LIKE ANEURYSM: A CASE REPORT

Author

Incandela F., Abrignani S., Geraci L., Gallo C., Gagliardo C., Craparo G., Incandela F., Abrignani S., Geraci L., Gallo C., Gagliardo C., and Craparo G.

Subjects
Ruptured Aneurysm, Endovascular Procedures, Interventional Radiology, Intracranial Aneurysm, Subarachnoid Hemorrhage
Abstract

Blister-like aneurysms (BLA) are a rare half-dome-shaped aneurysm, with a broad-based appearance, originating more often from a non-branching site of the supraclinoid internal carotid artery (ICA). They are sometimes difficult to recognize due to their morphological changes and high tendency to rupture. BLAs are often undiagnosed and may be detected only after repeated angiograms in the case of acute subarachnoid hemorrhage (SAH). BLA are life-threatening and no consensus has so far been reached on the best management strategy. We describe a patient with a BLA in the left ICA successfully treated by flow-diverting device using intraoperative abciximab bolus, with successful results. Recently, the use of flow-diverting device (FDD), has offered a very promising option for treatment even for ruptured BLA, with high long-term occlusion and low complication rates. However, double antiplatelet therapy is required and still represents a major constraint in a case of SAH, so that standardized multicenter studies are still needed.

Published
2021

17. Eomesodermin controls a unique differentiation program in human IL-10 and IFN-gamma coproducing regulatory T cells

Author

Gruarin, P, Maglie, S, De Simone, M, Haringer, B, Vasco, C, Ranzani, V, Bosotti, R, Noddings, J, Larghi, P, Facciotti, F, Sarnicola, M, Martinovic, M, Crosti, M, Moro, M, Rossi, R, Bernardo, M, Caprioli, F, Locatelli, F, Rossetti, G, Abrignani, S, Pagani, M, Geginat, J, Gruarin P, Maglie S, De Simone M, Haringer B, Vasco C, Ranzani V, Bosotti R, Noddings JS, Larghi P, Facciotti F, Sarnicola ML, Martinovic M, Crosti M, Moro M, Rossi RL, Bernardo ME, Caprioli F, Locatelli F, Rossetti G, Abrignani S, Pagani M, Geginat J, Gruarin, P, Maglie, S, De Simone, M, Haringer, B, Vasco, C, Ranzani, V, Bosotti, R, Noddings, J, Larghi, P, Facciotti, F, Sarnicola, M, Martinovic, M, Crosti, M, Moro, M, Rossi, R, Bernardo, M, Caprioli, F, Locatelli, F, Rossetti, G, Abrignani, S, Pagani, M, Geginat, J, Gruarin P, Maglie S, De Simone M, Haringer B, Vasco C, Ranzani V, Bosotti R, Noddings JS, Larghi P, Facciotti F, Sarnicola ML, Martinovic M, Crosti M, Moro M, Rossi RL, Bernardo ME, Caprioli F, Locatelli F, Rossetti G, Abrignani S, Pagani M, and Geginat J

Abstract

Whether human IL-10-producing regulatory T cells ("Tr1") represent a distinct differentiation lineage or an unstable activation stage remains a key unsolved issue. Here, we report that Eomesodermin (Eomes) acted as a lineage-defining transcription factor in human IFN-gamma/IL-10 coproducing Tr1-like cells. In vivo occurring Tr1-like cells expressed Eomes, and were clearly distinct from all other CD4(+) T-cell subsets, including conventional cytotoxic CD4(+) T cells. They expressed Granzyme (Gzm) K, but had lost CD40L and IL-7R expression. Eomes antagonized the Th17 fate, and directly controlled IFN-gamma and GzmK expression. However, Eomes binding to the IL-10 promoter was not detectable in human CD4(+) T cells, presumably because critical Tbox binding sites of the mouse were not conserved. A precommitment to a Tr1-like fate, i.e. concominant induction of Eomes, GzmK, and IFN-gamma, was promoted by IL-4 and IL-12-secreting myeloid dendritic cells. Consistently, Th1 effector memory cells contained precommitted Eomes(+)GzmK(+) T cells. Stimulation with T-cell receptor (TCR) agonists and IL-27 promoted the generation of Tr1-like effector cells by inducing switching from CD40L to IL-10. Importantly, CD4(+)Eomes(+) T-cell subsets were present in lymphoid and nonlymphoid tissues, and their frequencies varied systemically in patients with inflammatory bowel disease and graft-versus-host disease. We propose that Eomes(+) Tr1-like cells are effector cells of a unique GzmK-expressing CD4(+) T-cell subset.

Published
2019

18. Novel biomarkers for primary biliary cholangitis to improve diagnosis and understand underlying regulatory mechanisms

Author

Bombaci, M, Pesce, E, Torri, A, Carpi, D, Crosti, M, Lanzafame, M, Cordiglieri, C, Sinisi, A, DEL MORO, L, Bernuzzi, F, Gerussi, A, Geginat, J, Muratori, L, Terracciano, L, Invernizzi, P, Abrignani, S, Grifantini, R, Bombaci M., Pesce E., Torri A., Carpi D., Crosti M., Lanzafame M., Cordiglieri C., Sinisi A., DEL MORO, LILIA ANNA PAOLA MARIA, Bernuzzi F., Gerussi A., Geginat J., Muratori L., Terracciano L. M., Invernizzi P., Abrignani S., Grifantini R., Bombaci, M, Pesce, E, Torri, A, Carpi, D, Crosti, M, Lanzafame, M, Cordiglieri, C, Sinisi, A, DEL MORO, L, Bernuzzi, F, Gerussi, A, Geginat, J, Muratori, L, Terracciano, L, Invernizzi, P, Abrignani, S, Grifantini, R, Bombaci M., Pesce E., Torri A., Carpi D., Crosti M., Lanzafame M., Cordiglieri C., Sinisi A., DEL MORO, LILIA ANNA PAOLA MARIA, Bernuzzi F., Gerussi A., Geginat J., Muratori L., Terracciano L. M., Invernizzi P., Abrignani S., and Grifantini R.

Abstract

Background and aims: Primary biliary cholangitis is an autoimmune biliary disease characterized by injury of bile ducts, eventually leading to cirrhosis and death. In most cases, anti-mitochondrial antibodies and persistently elevated serum alkaline phosphatase are the basis for the serological diagnosis. Anti-nuclear antibodies are also useful and may indicate a more aggressive diseases course. In patients in which anti-mitochondrial antibodies are not detected, an accurate diagnosis requires liver histology. This study aims at identifying specific biomarkers for the serological diagnosis of primary biliary cholangitis. Methods: Sera from patients affected by primary biliary cholangitis, primary sclerosing cholangitis, hepatitis C virus (with and without cryoglobulinemia), hepatocarcinoma and healthy donors were tested on a protein array representing 1658 human proteins. The most reactive autoantigens were confirmed by DELFIA analysis on expanded cohorts of the same mentioned serum classes, and on autoimmune hepatitis sera, using anti-PDC-E2 as reference biomarker. Results: Two autoantigens, SPATA31A3 and GARP, showed high reactivity with primary biliary cholangitis sera, containing or not anti-mitochondrial antibodies. Their combination with PDC-E2 allowed to discriminate primary biliary cholangitis from all tested control classes with high sensitivity and specificity. We found that GARP expression is upregulated upon exposure to biliary salts in human cholangiocytes, an event involving EGFR and insulin pathways. GARP expression was also detected in biliary duct cells of PBC patients. Conclusions: This study highlighted SPATA31A3 and GARP as new biomarkers for primary biliary cholangitis and unravelled molecular stimuli underlying GARP expression in human cholangiocytes

Published
2019

19. Clonally expanded EOMES+ Tr1-like cells in primary and metastatic tumors are associated with disease progression

Author

Bonnal, R.J., Rossetti, G., Lugli, E., Simone, M. De, Gruarin, P., Brummelman, J., Drufuca, L., Passaro, M., Bason, R., Gervasoni, F., Chiara, G. Della, D'Oria, C., Martinovic, M., Curti, S., Ranzani, V., Cordiglieri, C., Alvisi, G., Mazza, E.M.C., Oliveto, S., Silvestri, Y., Carelli, E., Mazzara, S., Bosotti, R., Sarnicola, M.L., Godano, C., Bevilacqua, V., Lorenzo, M., Siena, S. Di, Bonoldi, E., Sartore-Bianchi, A., Amatu, A., Veronesi, G., Novellis, P., Alloisio, M., Giani, A., Zucchini, N., Opocher, E., Ceretti, A.P., Mariani, N., Biffo, S., Prati, D., Bardelli, A., Geginat, J., Lanzavecchia, A., Abrignani, S., Pagani, M., Bonnal, R.J., Rossetti, G., Lugli, E., Simone, M. De, Gruarin, P., Brummelman, J., Drufuca, L., Passaro, M., Bason, R., Gervasoni, F., Chiara, G. Della, D'Oria, C., Martinovic, M., Curti, S., Ranzani, V., Cordiglieri, C., Alvisi, G., Mazza, E.M.C., Oliveto, S., Silvestri, Y., Carelli, E., Mazzara, S., Bosotti, R., Sarnicola, M.L., Godano, C., Bevilacqua, V., Lorenzo, M., Siena, S. Di, Bonoldi, E., Sartore-Bianchi, A., Amatu, A., Veronesi, G., Novellis, P., Alloisio, M., Giani, A., Zucchini, N., Opocher, E., Ceretti, A.P., Mariani, N., Biffo, S., Prati, D., Bardelli, A., Geginat, J., Lanzavecchia, A., Abrignani, S., and Pagani, M.

Abstract

Item does not contain fulltext

Published
2021

21. POS0048 SEROPREVALENCE OF ANTI-SARS-COV-2 ANTIBODIES IN RHEUMATIC PATIENTS TREATED WITH BIOLOGICAL AND TARGETED THERAPY LIVING IN LOMBARDY, ITALY (MAINSTREAM PROJECT)

Author

Favalli, E. G., primary, Maioli, G., additional, Bombaci, M., additional, Biggioggero, M., additional, Favalli, A., additional, Agape, E., additional, Andrea, G., additional, Pesce, E., additional, Zagato, E., additional, Fabbris, T., additional, Martinovic, M., additional, Marchisio, E., additional, Abrignani, S., additional, Grifantini, R., additional, and Caporali, R., additional

Published
2021
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22. Intestinal IFN-gamma-producing type 1 regulatory T cells coexpress CCR5 and programmed cell death protein 1 and downregulate IL-10 in the inflamed guts of patients with inflammatory bowel disease

Author

Alfen, J, Larghi, P, Facciotti, F, Gagliani, N, Bosotti, R, Paroni, M, Maglie, S, Gruarin, P, Vasco, C, Ranzani, V, Frusteri, C, Iseppon, A, Moro, M, Crosti, M, Gatti, S, Pagani, M, Caprioli, F, Abrignani, S, Flavell, R, Geginat, J, Alfen JS, Larghi P, Facciotti F, Gagliani N, Bosotti R, Paroni M, Maglie S, Gruarin P, Vasco CM, Ranzani V, Frusteri C, Iseppon A, Moro M, Crosti MC, Gatti S, Pagani M, Caprioli F, Abrignani S, Flavell RA, Geginat J, Alfen, J, Larghi, P, Facciotti, F, Gagliani, N, Bosotti, R, Paroni, M, Maglie, S, Gruarin, P, Vasco, C, Ranzani, V, Frusteri, C, Iseppon, A, Moro, M, Crosti, M, Gatti, S, Pagani, M, Caprioli, F, Abrignani, S, Flavell, R, Geginat, J, Alfen JS, Larghi P, Facciotti F, Gagliani N, Bosotti R, Paroni M, Maglie S, Gruarin P, Vasco CM, Ranzani V, Frusteri C, Iseppon A, Moro M, Crosti MC, Gatti S, Pagani M, Caprioli F, Abrignani S, Flavell RA, and Geginat J

Abstract

Background: IL-10 is an anti-inflammatory cytokine required for intestinal immune homeostasis. It mediates suppression of T-cell responses by type 1 regulatory T (T(R)1) cells but is also produced by CD25(+) regulatory T (Treg) cells. Objective: We aimed to identify and characterize human intestinal T(R)1 cells and to investigate whether they are a relevant cellular source of IL-10 in patients with inflammatory bowel diseases (IBDs). Methods: CD4(+) T cells isolated from the intestinal lamina propria of human subjects and mice were analyzed for phenotype, cytokine production, and suppressive capacities. Intracellular IL-10 expression by CD4(+) T-cell subsets in the inflamed guts of patients with IBD (Crohn disease or ulcerative colitis) was compared with that in cells from noninflamed control subjects. Finally, the effects of proinflammatory cytokines on T-cell IL-10 expression were analyzed, and IL-1 beta and IL-23 responsiveness was assessed. Results: Intestinal T(R)1 cells could be identified by coexpression of CCR5 and programmed cell death protein 1 (PD-1) in human subjects and mice. CCR5(+) PD-1(+) T(R)1 cells expressed IFN-gamma and efficiently suppressed T-cell proliferation and transfer colitis. Intestinal IFN-gamma(+) T(R)1 cells, but not IL-7 receptor-positive T-H cells or CD25(+) Treg cells, showed lower IL-10 expression in patients with IBDs. T(R)1 cells were responsive to IL-23, and IFN-gamma(+) T(R)1 cells downregulated IL-10 with IL-1 beta and IL-23. Conversely, CD25(+) Treg cells expressed higher levels of IL-1 receptor but showed stable IL-10 expression. Conclusions: We provide the first ex vivo characterization of human intestinal T(R)1 cells. Selective downregulation of IL-10 by IFN-gamma(+) T(R)1 cells in response to proinflammatory cytokines is likely to drive excessive intestinal inflammation in patients with IBDs.

Published
2018

23. High-dose vitamin C enhances cancer immunotherapy

Author

Magri, A., Germano, G., Lorenzato, A., Lamba, S., Chila, R., Montone, M., Amodio, V., Ceruti, T., Sassi, F., Arena, S., Abrignani, S., D'Incalci, M., Zucchetti, M., Di Nicolantonio, F., Bardelli, A., and co-last and corresponding authors

Subjects
medicine.medical_treatment, PD-1 BLOCKADE, SOLID TUMORS, ASCORBATE, CELLS, DEMETHYLATION, CHEMOTHERAPY, STABILITY, NIVOLUMAB, VITAMIN C, IMMUNOTHERAPY, Antineoplastic Agents, Ascorbic Acid, DEMETHYLATION, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, Cancer immunotherapy, Tumor Microenvironment, medicine, Animals, Cytotoxic T cell, Melanoma, 030304 developmental biology, 0303 health sciences, Tumor microenvironment, STABILITY, business.industry, NIVOLUMAB, General Medicine, Immunotherapy, CHEMOTHERAPY, PD-1 BLOCKADE, SOLID TUMORS, Immune checkpoint, 3. Good health, VITAMIN C, ASCORBATE, 030220 oncology & carcinogenesis, CELLS, Cancer cell, Cancer research, Nivolumab, business
Abstract

Vitamin C (VitC) is known to directly impair cancer cell growth in preclinical models, but there is little clinical evidence on its antitumoral efficacy. In addition, whether and how VitC modulates anticancer immune responses is mostly unknown. Here, we show that a fully competent immune system is required to maximize the antiproliferative effect of VitC in breast, colorectal, melanoma, and pancreatic murine tumors. High-dose VitC modulates infiltration of the tumor microenvironment by cells of the immune system and delays cancer growth in a T cell-dependent manner. VitC not only enhances the cytotoxic activity of adoptively transferred CD8 T cells but also cooperates with immune checkpoint therapy (ICT) in several cancer types. Combination of VitC and ICT can be curative in models of mismatch repair-deficient tumors with high mutational burden. This work provides a rationale for clinical trials combining ICT with high doses of VitC.

Published
2020
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25. THU0221 EVIDENCE FOR A PATHOGENIC ROLE OF EXTRA-FOLLICULAR, IL-10 PRODUCING CCR6+B-HELPER T-CELLS IN SYSTEMIC LUPUS ERYTHEMATOSUS

Author

Gerosa, M., primary, Facciotti, F., additional, Larghi, P., additional, Bosotti, R., additional, Vasco, C., additional, Gagliani, N., additional, Cordiglieri, C., additional, Rottoli, E., additional, Penatti, A. E., additional, Argolini, L. M., additional, Karnani, B., additional, Kobayashi, Y., additional, Bombaci, M., additional, Van Hamburg, J. P., additional, Gualtierotti, R., additional, Gatti, S., additional, Torretta, S., additional, Pignataro, L., additional, Tas, S. W., additional, Caporali, R., additional, Abrignani, S., additional, Pagani, M., additional, Grassi, F., additional, Meroni, P. L., additional, Flavell, R., additional, and Geginat, J., additional

Published
2020
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26. Evidence for a pathogenic role of extrafollicular, IL-10–producing CCR6 + B helper T cells in systemic lupus erythematosus

Author

Facciotti, F., primary, Larghi, P., additional, Bosotti, R., additional, Vasco, C., additional, Gagliani, N., additional, Cordiglieri, C., additional, Mazzara, S., additional, Ranzani, V., additional, Rottoli, E., additional, Curti, S., additional, Penatti, A., additional, Karnani, B., additional, Kobayashi, Y., additional, Crosti, M., additional, Bombaci, M., additional, van Hamburg, J. P., additional, Rossetti, G., additional, Gualtierotti, R., additional, Gerosa, M., additional, Gatti, S., additional, Torretta, S., additional, Pignataro, L., additional, Tas, S. W., additional, Abrignani, S., additional, Pagani, M., additional, Grassi, F., additional, Meroni, P. L., additional, Flavell, R. A., additional, and Geginat, J., additional

Published
2020
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27. Differences in serum and synovial CD4+ T cells and cytokine profiles to stratify patients with inflammatory osteoarthritis and rheumatoid arthritis

Author

Penatti, A, Facciotti, F, De Matteis, R, Larghi, P, Paroni, M, Murgo, A, De Lucia, O, Pagani, M, Pierannunzii, L, Truzzi, M, Ioan-Facsinay, A, Abrignani, S, Geginat, J, Meroni, P, Penatti A, Facciotti F, De Matteis R, Larghi P, Paroni M, Murgo A, De Lucia O, Pagani M, Pierannunzii L, Truzzi M, Ioan-Facsinay A, Abrignani S, Geginat J, Meroni PL., Penatti, A, Facciotti, F, De Matteis, R, Larghi, P, Paroni, M, Murgo, A, De Lucia, O, Pagani, M, Pierannunzii, L, Truzzi, M, Ioan-Facsinay, A, Abrignani, S, Geginat, J, Meroni, P, Penatti A, Facciotti F, De Matteis R, Larghi P, Paroni M, Murgo A, De Lucia O, Pagani M, Pierannunzii L, Truzzi M, Ioan-Facsinay A, Abrignani S, Geginat J, and Meroni PL.

Abstract

Background: The aim was to investigate CD4+T-cell subsets, immune cells and their cytokine profiles in blood and synovial compartments in rheumatoid arthritis (RA) and inflammatory osteoarthritis (OA) to define specific immune signatures. Methods: Peripheral blood, synovial fluid (SF) and synovial membranes (SM) of RA and OA patients were analyzed. CD4+T-cell subset frequencies were determined by flow cytometry, and cytokine concentrations in serum and SF were measured by ELISA. Results: In peripheral blood, OA patients had altered frequencies of regulatory T-cell subsets, and higher frequencies of Th17 and of Th1/17 cells than RA patients. In the synovial compartment of OA patients, conventional Th17 cells were largely excluded, while Th1/17 cells were enriched and more frequent than in RA patients. Conversely, in the synovial compartment of RA patients, regulatory T cells and Tfh cells were enriched and more frequent then in OA patients. IL-17 and Blys were increased both in serum and SF of RA patients, and correlated with autoantibodies and disease activity. Notably, Blys levels were already significantly elevated in RA patients with low disease activity score in 28 joints (DAS28) and without autoantibody positivity. Conclusions: Although patients with inflammatory OA have immune activation in the synovial compartment, they display different T-cell subset frequencies and cytokine profiles. Soluble mediators such as Blys might help to discriminate mild clinical forms of RA from inflammatory OA particularly at the onset of the disease.

Published
2017

29. Immunology

Author

Shahi, C. N., Fou, X. J., Chua, A., McDevitt, T., O’Connell, M., Weir, D. G., Keeling, P. W. N., Kelleher, D., Crabtree, J. E., Lindley, I. J. D., Trejdosiewicz, L. K., Peichl, P., Wyatt, J.I, Figura, N., Tomkins, D. S., Bughol, M., Wyatt, J. I., Sobala, G. M., Primioc, J. N., Weigert, N., Stolley, S., Schusdziarra, V., Classen, M., Schepp, W., Kuipers, E. J., Gracia-Casanova, M., Pena, A. S., Crusius, J. B. A., Defize, J., van Kamp, G., Meuwissen, S. G. M., Pals, G., Ryan, E., Mac Mathuna, P., Kelly, P., Lennon, J., Crowe, J., Lynch, D. A. F., Mapstoe, N. M., Lewis, F., Hassan, F., Axon, A. T. R., Dixon, M. F., Quirke, P. E., Karttunen, R., Karttunen, T., Kerola, T., Niemlä, S., Kosunen, T. U., De Magistris, M. T., Nuti, S., Tommaso, A. Di, Figura, N., Bayel, P. F., Penhatini, C., Bugnoli, M., Rappuoli, R., Abrignani, S., Atherton, J. C., Hudson, N., Hale, T. L., Kirk, G. E., Spiller, R. C., Hawkey, C. J., Noach, L. A., Bosma, N. B., Jansen, J., Ceska, M., Tytgat, G. N. J., Deventer, S. J. H. van, Tulliez, M., Guerre, J., Orsini, E., Chaussade, S., Gaudric, M., Willemse, P. J. A., de Maat, M. P. M., Godfroy, F. J. M., Knot, E. A. R., Blankenstein, M.van, Wilson, J. H. P., Fan, X. J., and Keeling, P. W. N.

Published
1992
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30. Abstract form for the Irish Journal of Medical Science v workshop on gastroduodenal pathology and Helicobacter pylori July 5th — 7th 1992 — Dublin, Ireland

Author

Logan, R. P. H., Gummett, P. A., Walker, M. M., Karim, Q. N., Baron, J. H., Misiewicz, J. J., Trieber, G., Walker, S., Klotz, U., Lozniewski, A., Weber, M., de Korwin, J. D., Floquet, J., Conroy, M. C., Burdin, J. C., Mannes, G. A., Bayerdörffer, E., Höchter, W., Weingart, J., Heldwein, W., Sommer, A., Müller-Lissner, S., Bomschein, W., Miehlke, S., Weinzierl, M., Ruckdeschel, G., von Wulffen, H., Köpcke, W., Stolte, M., Rune, S. J., Justesen, T., Hansen, J. M., Jensen, T. G., Eriksen, J., Thomsen, O. ø., Scheibel, J., Bonnevie, O., Bremmelgaard, A., Vilien, M., Knuhtsen, S., Elsborg, L., Hansen, J., Lauritsen, K., Wulff, H. R., Boixeda, D., Ballestero, S., Cantón, R., De Rafael, L., Martinm de Argila, C., Pozuelo, M. J., Sampedro, J., Baquero, F., Grigoriev, P. Ya., Isakov, V. A., Iakovenko, E. P., Hirschl, A. M., Brandstätter, G., Dragosics, B., Hentschel, E., Kundi, M., Rotter, M. L., Schütze, K., Taufer, M., Neri M, Susi D, Bovani I, Pindo R, Cuccurullo F., Coelho, L. G. V., Passos, M. C. F., Chausson, Y., Vieira, W. L. S., Castro, F. J., Franco, J. M. M., Fernandes, M. L. M., Castro, L. P., Jonas, C., De Koster, E., Van Gossum, M., Depierreux, M., Cheval, M., Deltenre, M., Schütz, E., Bethke, B., Lee, A., Hegedus, E., O’Rourke, J., Larsson, H., Sjöstedt, S., Veress, B., Nord, C. E., Sobala, G. M., George, R., Tompkins, D., Finlay, J., Manning, A., Sant, S., Xia, H. X., Daw, M., Gilvarry, J., Keane, C. T., O’Morain, C., Rubio, M. A., Hegarty, B., Blum, A. L., Sulser, E., Stadelmann, O., Munoz, N., Buiatti, E., Vivas, J., Oliver, W., Cano, E., Peraza, S., Castro, D., Sanchez, V., Andrade, O., Benz, M., Mendz, G. L., Hazell, S. L., Salmela, K. S., Roire, R. P., Hook-Nikanne, J., Kosunen, T. U., Salaspur, M., Luke, C. J., Reynolds, D. D. J., Penn, C. W., Bode, G., Mauch, F., Ditschuneit, H., Malfertheiner, P., Ferrero, Richard L., Agnes Labigne, Eaton, K. A., Krakowka, S., Mobley, H. L. T., Hu, Li-Tai, Foxall, P. A., Moran, A. P., Helander, I. M., Altman, C., Sobhani, I., Vissugaire, C., Migrant, M., Etienne, J. P., Sommi, P., Ricci, V., Fiocca, R., Cova, E., Figura, N., Romano, M., Ivey, K. J., Solcia, E., Ventura, U., Nilius, M., Schieffer, S., Hengels, K. J., Jablonowski, H., Strohmeyer, G., Cabrai, M. D., Barbosa, A. J. A., Lima Hr., G. F., Oliveira, C. A., Polak, J. M., Oderda, G., Villani, L., Altare, F., Morra, I., Miserendino, L., Ansaldi, N., Dixon, M. F., Wyatt, J. I., Axon, A. T. R., Beattie, S., Hamilton, H., Shabib, S., Cutz, E., Drumm, B., Sherman, P., Noach, L. A., Rolf, T., Bosma, N. B., Schwartz, M. P., Oosting, J., Rauws, E. A. J., Tytgat, G. N. J., Andrew, A., Nardone, G., d’Ormiento, F., Pontillo, M., Lobo, A. J., Uff, J. S., McNulty, C. N. M., Wilkinson, S. P., Suriani, R., Pallante, C., Ravizza, M., Galliano, D., Sallio, D., Malandrino, M., Oneglio, R., Colozza, M., Mazzucco, D., Gaia, E., Eidt, S., Vincent, P., Gottrand, F., Turck, D., Lecomte-Houcke, M., Leclerc, H., Bonvicini, F., Pretolani, S., Baraldini, M., Cilla, D., Baldinelli, S., Bazocchi, E., Acampora, P., Careddu, N., Brocchi, E., Gasbarrini, G., Joubert, M., Bazin, N., Thiaucourt, D., Protte, E., Gissler, C., Duprez, A., Merlin, P., Forestier, S., Labenz, J., Gyenes, E., Rühl, G. H., Börsch, G., Daskalopoulos, G., Carrick, J., Lian, R., Wagner, S., Bleck, J., Gebel, M., Bär, W., Manns, M., Lamouliatte, H., Bernard, P. H., Cayla, R., Vialette, G., Quinton, A., Mégraud, F., Lemaire, M., Quinten, A., De Mascarel, A., Webb, P., Forman, D., Knight, T., Wilson, A., Graves, S., Newell, D., Elder, J., Tonelli, E., Gatte, M. R. A., Ghironzi, G. C., Giulianelli, G., Bamford, K. B., Collins, J. S. A., Bickley, J., Johnston, B. T., Potts, S., Boston, V., Owen, R. J., Sloan, J., Basso, L., Lawlor, S., Clune, J., Szelényi, H., Stohmeyer, G., Macedo, G., Iglésias, I., Chaves, A. P., Loureiro, A., Katelaris, P. H., Seow, F., Lin, B., Napoli, J., Hones, D. B., Ngu, M. C., Akopyantz, Natalia S., Bukanov, Nikolay O., Westblom, T. Ulf, Berg, Douglas E., Nyst, J. F., Denis, P., Buset, M., De Reuck, M., Nielsen, H., Andersen, L. P., Birkholz, Sabine, Knipp, Ulrich, Nietzki, Claudia, Opferkuch, Wolfgang, Crabtree, J. E., Peichl, P., Lindly, I. J. D., Deusch, K., Seifirth, C., Funk, A., Dahie, I., Reut, K., Classen, M., Gionchetti, P., Vaira, D., Campieri, M., Bertinelli, E., Menegatti, M., Belluzzi, A., Briognola, C., Miglioli, M., Barbara, L., Tommaso, A. Di, Magistris, M. T. De, Bugnoli, M., Petracca, R., Covacci, A., Censini, S., Rappuoli, R., Abrignani, S., Territo, M. C., Smela, K. L., Reeve, J. R., Lee, T. D., Walsh, J. H., Armellini, D., Crabtree, J. E., Xiang, Z. Y., Mitchell, H. M., Hu, P. J., Li, Y. Y., Wang, Z. J., Zhao, S. M., Liu, Q., Chen, M., Du, G. G., Filipe, M. I., Reed, P. I., Craanen, M. E., Blok, P., Dekker, W., Colombo, E., Redaelli, D., Santangelo, M., Spinelli, M., Farinati, F., Valiante, F., Delia Libera, G., Germanà, B., Baffa, R., Rugge, M., Vianelo, F., Di Mario, F., Sipponen, Pentti, Rokkas, T., Popotheodorou, G., Kaldgeropoulos, N., Deprez, C., Galand, P., Fox, J. G., Wishnok, P., Murphy, J. C., Tannenbaum, S., Correa, P., Parsonnet, Julie, Macor, C., Da Broi, G. L., Avellinio, C., Reifen, R., Rasooly, I., Millson, M. E., Murphy, K., Thomas, J. E., Eastham, E. J., Malorgio, E., Dell’Olio, D., Kemmer, T. P., Dominguez-Munoz, J. E., Klingel, H., Gatto, M. R. A., Olivieri, R., Bayeli, R. F., Abate, L., De Gregorio, L., Aziz, J., Esposito, E., Basagni, C., Guilluy, R., Rousseau-Tsangaris, M., Brazier, J. L., Wadstiöm, Torkel, Tyszkiewicz, Tadeusz, Bergenzaun, Per, Olsson, Karin, Birac, C., Tall, F., Albenque, M., Labigne, A., Megraud, F., Feldman, R. A., Deeks, J., Glupczynski, Y., Burette, A., Goossens, H., Van den Boore, C., Butzler, J. P., Veldhuyzen van Zanten, S., Best, L., Benzanson, G., Haldane, D., Hazell, S., Mapstone, N. P., Lynch, D. A. F., Quirke, P., Taylor, D. E., Chang, N., Eaton, M., Stockdale, E., Salama, S. M., Thompson, L., Cockayne, A., Spiller, R. C., Leen, E., Sweeney, E., Klann, H., Hatz, R., Bornschein, W., Simon, T., Eimiller, A., Bolle, F., Schweikert, C., Köpeke, W., Moss, S. F., Bishop, A. E., Calam, J., Cahill, R. J., Xia, H., Solnick, J., and Tompkins, L.

Published
1992
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32. IL-10-producing forkhead box protein 3-negative regulatory T cells inhibit B-cell responses and are involved in systemic lupus erythematosus

Author

Facciotti, F, Gagliani, N, Häringer, B, Alfen, J, Penatti, A, Maglie, S, Paroni, M, Iseppon, A, Moro, M, Crosti, M, Stölzel, K, Romagnani, C, Moroni, G, Ingegnoli, F, Torretta, S, Pignataro, L, Annoni, A, Russo, F, Pagani, M, Abrignani, S, Meroni, P, Flavell, R, Geginat, J, Facciotti F, Gagliani N, Häringer B, Alfen JS, Penatti A, Maglie S, Paroni M, Iseppon A, Moro M, Crosti MC, Stölzel K, Romagnani C, Moroni G, Ingegnoli F, Torretta S, Pignataro L, Annoni A, Russo F, Pagani M, Abrignani S, Meroni P, Flavell R, Geginat J, Facciotti, F, Gagliani, N, Häringer, B, Alfen, J, Penatti, A, Maglie, S, Paroni, M, Iseppon, A, Moro, M, Crosti, M, Stölzel, K, Romagnani, C, Moroni, G, Ingegnoli, F, Torretta, S, Pignataro, L, Annoni, A, Russo, F, Pagani, M, Abrignani, S, Meroni, P, Flavell, R, Geginat, J, Facciotti F, Gagliani N, Häringer B, Alfen JS, Penatti A, Maglie S, Paroni M, Iseppon A, Moro M, Crosti MC, Stölzel K, Romagnani C, Moroni G, Ingegnoli F, Torretta S, Pignataro L, Annoni A, Russo F, Pagani M, Abrignani S, Meroni P, Flavell R, and Geginat J

Published
2016

34. HCV E1E2-MF59 vaccine in chronic hepatitis C patients treated with PEG-IFNα2a and Ribavirin: a randomized controlled trial

Author

Almasio, P., Colombatto, P., Brunetto, M., Maina, A., Romagnoli, V., Rumi, M., Ascione, A., Pinzello, G., Mondelli, M., Muratori, L., Rappuoli, R., Rosa, D., Houghton, M., Abrignani, S., Bonino, F., Almasio, PL, Colombatto, P, Brunetto, MR, Maina, AM, Romagnoli, V, Almasio, P, Rumi, MG, Ascione, A, Pinzello, G, Mondelli, M, Muratori, L, Rappuoli, R, Rosa, D, Houghton, M, Abrignani, S, and Bonino, F

Subjects
HCV vaccine
Abstract

Hepatitis C virus (HCV) vaccines may be able to increase viral clearance in combination with antiviral therapy. We analysed viral dynamics and HCV-specific immune response during retreatment for experienced patients in a phase Ib study with E1E2MF59 vaccine. Seventy-eight genotype 1a/1b patients [relapsers (30), partial responders (16) and nonresponders (32) to interferon-(IFN)/ribavirin-(RBV)] were randomly assigned to vaccine (V:23), Peg-IFNα2a-180-ug/qw and ribavirin 1000-1200-mg/qd for 48 weeks (P/R:25), or their combination (P/R + V:30). Vaccine (100 μg/0.5 mL) was administered intramuscularly at week 0-4-8-12-24-28-32-36. Neutralizing of binding (NOB) antibodies and lymphocyte proliferation assay (LPA) for E1E2-specific-CD4 + T cells were performed at week 0-12-16-48. Viral kinetics were analysed up to week 16. The vaccine was safe, and a sustained virological response (SVR) was achieved in 4 P/R + V and 2 P/R patients. Higher SVR rates were observed in prior relapsers (P/R + V = 27.3%; P/R = 12.5%). Higher NOB titres and LPA indexes were found at week 12 and 16 in P/R + V as compared to P/R patients (P = 0.023 and 0.025, P = 0.019 and

Published
2014

35. Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells

Author

De Simone, M., Arrigoni, A., Rossetti, G., Gruarin, P., Ranzani, V., Politano, C., Bonnal, R.J., Provasi, E., Sarnicola, M.L., Panzeri, I., Moro, M., Crosti, M., Mazzara, S., Vaira, V., Bosari, S., Palleschi, A., Santambrogio, L., Bovo, G., Zucchini, N., Totis, M., Gianotti, L., Cesana, G., Perego, R.A., Maroni, N., Pisani Ceretti, A., Opocher, E., De Francesco, R., Geginat, J., Stunnenberg, H., Abrignani, S., Pagani, M., De Simone, M., Arrigoni, A., Rossetti, G., Gruarin, P., Ranzani, V., Politano, C., Bonnal, R.J., Provasi, E., Sarnicola, M.L., Panzeri, I., Moro, M., Crosti, M., Mazzara, S., Vaira, V., Bosari, S., Palleschi, A., Santambrogio, L., Bovo, G., Zucchini, N., Totis, M., Gianotti, L., Cesana, G., Perego, R.A., Maroni, N., Pisani Ceretti, A., Opocher, E., De Francesco, R., Geginat, J., Stunnenberg, H., Abrignani, S., and Pagani, M.

Abstract

Contains fulltext : 161837.pdf (publisher's version ) (Open Access), Tumor-infiltrating regulatory T lymphocytes (Treg) can suppress effector T cells specific for tumor antigens. Deeper molecular definitions of tumor-infiltrating-lymphocytes could thus offer therapeutic opportunities. Transcriptomes of T helper 1 (Th1), Th17, and Treg cells infiltrating colorectal or non-small-cell lung cancers were compared to transcriptomes of the same subsets from normal tissues and validated at the single-cell level. We found that tumor-infiltrating Treg cells were highly suppressive, upregulated several immune-checkpoints, and expressed on the cell surfaces specific signature molecules such as interleukin-1 receptor 2 (IL1R2), programmed death (PD)-1 Ligand1, PD-1 Ligand2, and CCR8 chemokine, which were not previously described on Treg cells. Remarkably, high expression in whole-tumor samples of Treg cell signature genes, such as LAYN, MAGEH1, or CCR8, correlated with poor prognosis. Our findings provide insights into the molecular identity and functions of human tumor-infiltrating Treg cells and define potential targets for tumor immunotherapy.

Published
2016

36. Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells

Author

De Simone, M, Arrigoni, A, Rossetti, G, Gruarin, P, Ranzani, V, Politano, C, Bonnal, R, Provasi, E, Sarnicola, M, Panzeri, I, Moro, M, Crosti, M, Mazzara, S, Vaira, V, Bosari, S, Palleschi, A, Santambrogio, L, Bovo, G, Zucchini, N, Totis, M, Gianotti, L, Cesana, G, Perego, R, Maroni, N, Pisani Ceretti, A, Opocher, E, De Francesco, R, Geginat, J, Stunnenberg, H, Abrignani, S, Pagani, M, Bonnal, RJP, Sarnicola, ML, Perego, RA, Stunnenberg, HG, De Simone, M, Arrigoni, A, Rossetti, G, Gruarin, P, Ranzani, V, Politano, C, Bonnal, R, Provasi, E, Sarnicola, M, Panzeri, I, Moro, M, Crosti, M, Mazzara, S, Vaira, V, Bosari, S, Palleschi, A, Santambrogio, L, Bovo, G, Zucchini, N, Totis, M, Gianotti, L, Cesana, G, Perego, R, Maroni, N, Pisani Ceretti, A, Opocher, E, De Francesco, R, Geginat, J, Stunnenberg, H, Abrignani, S, Pagani, M, Bonnal, RJP, Sarnicola, ML, Perego, RA, and Stunnenberg, HG

Abstract

Tumor-infiltrating regulatory T lymphocytes (Treg) can suppress effector T cells specific for tumor antigens. Deeper molecular definitions of tumor-infiltrating-lymphocytes could thus offer therapeutic opportunities. Transcriptomes of T helper 1 (Th1), Th17, and Treg cells infiltrating colorectal or non-small-cell lung cancers were compared to transcriptomes of the same subsets from normal tissues and validated at the single-cell level. We found that tumor-infiltrating Treg cells were highly suppressive, upregulated several immune-checkpoints, and expressed on the cell surfaces specific signature molecules such as interleukin-1 receptor 2 (IL1R2), programmed death (PD)-1 Ligand1, PD-1 Ligand2, and CCR8 chemokine, which were not previously described on Treg cells. Remarkably, high expression in whole-tumor samples of Treg cell signature genes, such as LAYN, MAGEH1, or CCR8, correlated with poor prognosis. Our findings provide insights into the molecular identity and functions of human tumor-infiltrating Treg cells and define potential targets for tumor immunotherapy.

Published
2016

37. HCV E1E2-MF59vaccine in chronic hepatitis C patients treated with PEG-IFNα2a and Ribavirin: a randomized controlled trial

Author

Colombatto, P, Brunetto, M R, Maina, A M, Romagnoli, V, Almasio, P, Rumi, M G, Ascione, A, Pinzello, G, Mondelli, M, Muratori, L, Rappuoli, R, Rosa, D, Houghton, M, Abrignani, S, Bonino, F, P. Colombatto, M. R. Brunetto, A. M. Maina, V. Romagnoli, P. Almasio, M. G. Rumi, A. Ascione, G. Pinzello, M. Mondelli, L. Muratori, R. Rappuoli, D. Rosa, M. Houghton, S. Abrignani, and F. Bonino

Subjects
CD4-Positive T-Lymphocytes, Squalene, Viral Hepatitis Vaccines, Drug-Related Side Effects and Adverse Reactions, viral kinetics, Polysorbates, VACCINE, Antiviral Agents, Injections, Intramuscular, immune response, Polyethylene Glycols, viral kinetic, Adjuvants, Immunologic, Ribavirin, Humans, neutralizing antibodies, HCV, interferon, vaccine, Cell Proliferation, Vaccines, Synthetic, Interferon-alpha, Original Articles, Hepatitis C Antibodies, Hepatitis C, Chronic, Viral Load, Antibodies, Neutralizing, Combined Modality Therapy, Recombinant Proteins, Treatment Outcome, RNA, Viral
Abstract

Hepatitis C virus (HCV) vaccines may be able to increase viral clearance in combination with antiviral therapy. We analysed viral dynamics and HCV-specific immune response during retreatment for experienced patients in a phase Ib study with E1E2MF59 vaccine. Seventy-eight genotype 1a/1b patients [relapsers (30), partial responders (16) and nonresponders (32) to interferon-(IFN)/ribavirin-(RBV)] were randomly assigned to vaccine (V:23), Peg-IFNα2a-180-ug/qw and ribavirin 1000–1200-mg/qd for 48 weeks (P/R:25), or their combination (P/R + V:30). Vaccine (100 μg/0.5 mL) was administered intramuscularly at week 0-4-8-12-24-28-32-36. Neutralizing of binding (NOB) antibodies and lymphocyte proliferation assay (LPA) for E1E2-specific-CD4 + T cells were performed at week 0-12-16-48. Viral kinetics were analysed up to week 16. The vaccine was safe, and a sustained virological response (SVR) was achieved in 4 P/R + V and 2 P/R patients. Higher SVR rates were observed in prior relapsers (P/R + V = 27.3%; P/R = 12.5%). Higher NOB titres and LPA indexes were found at week 12 and 16 in P/R + V as compared to P/R patients (P = 0.023 and 0.025, P = 0.019 and

Published
2014

38. The combination of IFN-lambda-4 and HLA-DPB1 polymorphisms accurately predict HBsAg loss in IFN treated genotype D HBeAg-negative patients with chronic hepatitis B

Author

Lampertico, P., primary, Galmozzi, E., additional, Facchetti, F., additional, Cheroni, C., additional, Invernizzi, F., additional, Valveri, V., additional, Soffredini, R., additional, Viganò, M., additional, Abrignani, S., additional, De Francesco, R., additional, and Colombo, M., additional

Published
2016
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42. NS5A Inhibitors Impair NS5A–Phosphatidylinositol 4-Kinase IIIα Complex Formation and Cause a Decrease of Phosphatidylinositol 4-Phosphate and Cholesterol Levels in Hepatitis C Virus-Associated Membranes

Author

Reghellin, V., primary, Donnici, L., additional, Fenu, S., additional, Berno, V., additional, Calabrese, V., additional, Pagani, M., additional, Abrignani, S., additional, Peri, F., additional, De Francesco, R., additional, and Neddermann, P., additional

Published
2014
Full Text
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47. Vdelta1 T lymphocytes expressing a Th1 phenotype are the major gammadelta T cell subset infiltrating the liver of HCV-infected persons

Author

Agrati C, D'Offizi G, Narciso P, Abrignani S, Giuseppe Ippolito, Colizzi V, and Poccia F

Subjects
Adult, Male, Protein Tyrosine Phosphatase, Non-Receptor Type 1, Receptors, Antigen, T-Cell, gamma-delta, CD8-Positive T-Lymphocytes, Middle Aged, Th1 Cells, Hepatitis C, Liver, T-Lymphocyte Subsets, Cytokines, Humans, Leukocyte Common Antigens, Female, L-Selectin, Research Article
Abstract

BACKGROUND: Hepatitis C infection induces an acute and chronic liver inflammation that may lead to cirrhosis, liver failure, or hepatocarcinoma. Since the role of alphabeta T lymphocytes in hepatitis C virus (HCV) immunopathology has been analyzed extensively, we investigated the distribution and functional activation of gammadelta T cell subsets in chronically HCV-infected patients. MATERIALS AND METHODS: Blood samples and liver biopsies from 35 patients with compensated chronic HCV infection were compared in terms of T cell subset distribution, expression of activation markers, gammadelta T cell receptor (TCR) repertoire, and pattern of cytokine production. Moreover, we analyzed whether these immunological parameters were associated with other clinical observations (plasma viremia, ALT levels, Ishak index). RESULTS: Differing from peripheral blood distribution, a specific compartmentalization of Vdelta1 T cells (p < 0.001) was observed in the liver of HCV patients. These cells represented a relevant fraction of intrahepatic T lymphocytes (1.8-8.7%) and expressed the memory/effector phenotype (CD62-L- CD45-RO+CD95+). This phenotype was consistent with selective homing upon antigen recognition. Mitogenic stimulation of Vdelta1 + T lymphocytes recruited in the liver revealed the T helper cell type 1 (Th1) pattern of cytokine secretion. Interestingly, the frequency of interferon-gamma (IFN-gamma)-producing Vdelta1 T cells was associated with an higher degree of liver necroinflammation, measured by the Ishak index. Finally, the T-cell repertoire analysis revealed the absence of Vgamma selection in the TCR repertoire of intrahepatic Vdelta1 T cells. CONCLUSIONS: gammadelta T cell distribution in the peripheral blood differs from the Vdelta1 T cell subset because it is policlonally activated and recruited in the liver of chronic HCV-infected patients. During HCV-infection, this T cell subset may release Th1 cytokines and contribute to the necroinflammatory liver disease.

Published
2001

49. HCV E1E 2‐ MF 59vaccine in chronic hepatitis C patients treated with PEG ‐ IFN α2a and R ibavirin: a randomized controlled trial

Author

Colombatto, P., primary, Brunetto, M. R., additional, Maina, A. M., additional, Romagnoli, V., additional, Almasio, P., additional, Rumi, M. G., additional, Ascione, A., additional, Pinzello, G., additional, Mondelli, M., additional, Muratori, L., additional, Rappuoli, R., additional, Rosa, D., additional, Houghton, M., additional, Abrignani, S., additional, and Bonino, F., additional

Published
2013
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