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1. Amnion responses to intrauterine inflammation and effects of inhibition of TNF signaling in preterm Rhesus macaque

Author

Pietro Presicce, Monica Cappelletti, Marco Morselli, Feiyang Ma, Paranthaman Senthamaraikannan, Giulia Protti, Brian B. Nadel, Laila Aryan, Mansoureh Eghbali, Lukasz Salwinski, Neema Pithia, Emily De Franco, Lisa A. Miller, Matteo Pellegrini, Alan H. Jobe, Claire A. Chougnet, and Suhas G. Kallapur

Subjects
Immunology, Bioinformatics, Omics, Science
Abstract

Summary: Intrauterine infection/inflammation (IUI) is a frequent complication of pregnancy leading to preterm labor and fetal inflammation. How inflammation is modulated at the maternal-fetal interface is unresolved. We compared transcriptomics of amnion (a fetal tissue in contact with amniotic fluid) in a preterm Rhesus macaque model of IUI induced by lipopolysaccharide with human cohorts of chorioamnionitis. Bulk RNA sequencing (RNA-seq) amnion transcriptomic profiles were remarkably similar in both Rhesus and human subjects and revealed that induction of key labor-mediating genes such as IL1 and IL6 was dependent on nuclear factor κB (NF-κB) signaling and reversed by the anti-tumor necrosis factor (TNF) antibody Adalimumab. Inhibition of collagen biosynthesis by IUI was partially restored by Adalimumab. Interestingly, single-cell transcriptomics, flow cytometry, and immunohistology demonstrated that a subset of amnion mesenchymal cells (AMCs) increase CD14 and other myeloid cell markers during IUI both in the human and Rhesus macaque. Our data suggest that CD14+ AMCs represent activated AMCs at the maternal-fetal interface.

Published
2023
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2. Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention

Author

Roberta Pastorino, Eloisa Arbustini, Andrea Faini, Gianfranco Parati, Grzegorz Bilo, Davide Soranna, Antonella Zambon, Sergio Leonardi, Alessandro Gialluisi, Lorenzo Giovanni Mantovani, Walter Ricciardi, Fabio Blandini, Giovanni Scambia, Catherine Klersy, Marialaura Bonaccio, Augusto Di Castelnuovo, Simona Costanzo, Amalia De Curtis, Mariarosaria Persichillo, Chiara Cerletti, Maria Benedetta Donati, Licia Iacoviello, Giuseppe Remuzzi, Camilla Torlasco, Giuseppe Ambrosio, Gabriele Zoppoli, Maria Chiara Grimaldi, Daniela Pedicino, Giovanna Liuzzo, Serena Pelusi, Daniele Prati, Luca Valenti, Francesca Gorini, Maurizio Sanguinetti, Giuseppe Ferrante, Gianluigi Condorelli, Giulio Pompilio, Stefania Boccia, Luigi Badano, Victor Savevski, Tiziana Bachetti, Gian Franco Gensini, Silvano Bosari, Alice Bonanni, Elena Tremoli, Angelo Santoliquido, Stefano Genovese, Sara Boveri, Gianfranco Gensini, Francesco Gianfagna, Italo Porto, Fabio Tuzzolino, Carolina Lombardi, Egidio Traversi, Fabrizio Veglia, Andrea Urbani, Domenico D’Amario, Gaetano Antonio Lanza, Antonio Uccelli, José Pablo Werba, Livio Luzi, Pietro Ameri, Davide Gentilini, Luisa Gilardini, Cecilia Invitti, Maurizio Volterrani, Maria Teresa La Rovere, Giovanni Gentile, Francesco Clemenza, Mario Urtis, Francesca Ieva, Maria Carla Roncaglioni, Valentina Milani, Paola Baiardi, Debora Rosa, Fabiana Madotto, Emilia Ruggiero, Teresa Panzera, Simona Esposito, Sara Magnacca, Fabrizia Noro, Roberta Parisi, Francesca Bracone, Irene Baroni, Damiano Baldassarre, Roberta Baetta, Luigi Frati, Pier Giulio Conaldi, Massimo Fini, Antonio Di Malta, Mauro Amato, Alice Bonomi, Francesca Colazzo, Martino Pengo, Luciana Auteri, Marta Baviera, Alberico Catapano, Alexis Elias Malavazos, Serenella Castelvecchio, Massimiliano Marco Corsi-Romanelli, Rosanna Cardani, Valentina Agnese, Bianca Pane, Laura Spinardi, Marco Visconti, Anna Di Blasio, Luisa Ojeda-Fernández, Andreana Foresta, Simonetta Scalvini, Antonia Pierobon, Alessandra Gorini, Annarosa Racca, Manuela Bandi, Lorenzo Menicanti, Gualtiero Colombo, Chiara Vavassori, Maria Luisa Biondi, Beatrice Frigerio, Alessio Ravani, Daniela Sansaro, Daniela Coggi, Alessandra Romandini, Monica Giroli, Mattia Giuliani, Maurizio Rondinelli, Catia Trudu, Carmen Cinieri, Massimo Monturano, Elisa Perger, Lucia Zanotti, Lidia Cova, Luca Grappiolo, Laura Papa, Ignazio Romano, Luisa Ojeda, Fiorenza Clerici, Angela Palumbo, Roberto Mattioli, Ermanno Longhi, Anwal Ghulam, Sabatino Orlandi, Sabrina Franciosa, Martina Morelli, Fiorella De Rita, Giovanni de Gaetano, Massimiliano MarcoCorsi Romanelli, Ambra Cerri, Carola Dubini, Manuel Bruno Trevisan, Laura Valentina Renna, Paola Giubbilini, Lucia Ramputi, Giada DeAngeli, Francesca Olmetti, Maurizio Bussotti, Carlo Gaetano, Martina Balbi, Laura Comini, Monica Lorenzoni, Adriana Olivares, Camilla Garrè, Riccardo Sideri, Giuseppe Caruana, Nicola Cuscino, Gabriele Di Gesaro, Alessio Greco, Italia Loddo, Domenico Palombo, Giovanni Spinella, Gaddiel Mozzetta, Alice Finotello, Giovanni Pratesi, Margherita Clerici, Cristiana Bianco, Rossana Carpani, Giulia Periti, Sara Margarita, Anna Severino, Alessia D’Aiello, Ramona Vinci, Mattia Brecciaroli, Simone Filomia, Luca Proto, Dalila Tarquini, Arianna Elia, Alessia Currao, Alessandro Di Toro, Lorenzo Giuliani, Giuseppe Caminiti, Federica Marcolongo, Barbara Sposato, Fiorella Guadagni, Valentina Morsella, Angelica Marziale, and Giulia Protti

Subjects
Medicine
Abstract

Introduction Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking.Methods and analysis The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners’ offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed.Ethics and dissemination This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study’s course and findings through regular meetings.Trial registration number NCT05339841.

Published
2023
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3. iNKT cell-neutrophil crosstalk promotes colorectal cancer pathogenesis

Author

Georgia Lattanzi, Francesco Strati, Angélica Díaz-Basabe, Federica Perillo, Chiara Amoroso, Giulia Protti, Maria Rita Giuffrè, Luca Iachini, Alberto Baeri, Ludovica Baldari, Elisa Cassinotti, Michele Ghidini, Barbara Galassi, Gianluca Lopez, Daniele Noviello, Laura Porretti, Elena Trombetta, Eleonora Messuti, Luca Mazzarella, Giandomenica Iezzi, Francesco Nicassio, Francesca Granucci, Maurizio Vecchi, Flavio Caprioli, Federica Facciotti, Lattanzi, G, Strati, F, Díaz-Basabe, A, Perillo, F, Amoroso, C, Protti, G, Rita Giuffrè, M, Iachini, L, Baeri, A, Baldari, L, Cassinotti, E, Ghidini, M, Galassi, B, Lopez, G, Noviello, D, Porretti, L, Trombetta, E, Messuti, E, Mazzarella, L, Iezzi, G, Nicassio, F, Granucci, F, Vecchi, M, Caprioli, F, and Facciotti, F

Subjects
Settore MED/12 - Gastroenterologia, Fusobacterium nucleatum, neutrophils, Immunology, MED/04 - PATOLOGIA GENERALE, CRC, iNKT cells, iNKT cell, Immunology and Allergy
Abstract

iNKT cells account for a relevant fraction of effector T-cells in the intestine and are considered an attractive platform for cancer immunotherapy. Although iNKT cells are cytotoxic lymphocytes, their functional role in colorectal cancer (CRC) is still controversial, limiting their therapeutic use. Thus, we examined the immune cell composition and iNKT cell phenotype of CRC lesions in patients (n = 118) and different murine models. High-dimensional single-cell flow-cytometry, metagenomics, and RNA sequencing experiments revealed that iNKT cells are enriched in tumor lesions. The tumor-associated pathobiont Fusobacterium nucleatum induces IL-17 and Granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in iNKT cells without affecting their cytotoxic capability but promoting iNKT-mediated recruitment of neutrophils with polymorphonuclear myeloid-derived suppressor cells-like phenotype and functions. The lack of iNKT cells reduced the tumor burden and recruitment of immune suppressive neutrophils. iNKT cells in-vivo activation with α-galactosylceramide restored their anti-tumor function, suggesting that iNKT cells can be modulated to overcome CRC-associated immune evasion. Tumor co-infiltration by iNKT cells and neutrophils correlates with negative clinical outcomes, highlighting the importance of iNKT cells in the pathophysiology of CRC. Our results reveal a functional plasticity of iNKT cells in CRC, suggesting a pivotal role of iNKT cells in shaping the tumor microenvironment, with relevant implications for treatment.

Published
2023

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