Search

Your search keyword '"Krzewski, Konrad"' showing total 148 results
Start Over Author "Krzewski, Konrad"
148 results on '"Krzewski, Konrad"'

1. Efficacy of T-cell assays for the diagnosis of primary defects in cytotoxic lymphocyte exocytosis

Author

Abboud, Miguel R, Aytac, Sevkiye Selin, Bosse, Franziskus Johannes, Choo, Sharon, Drabko, Katarzyna, Onkologii, Klinika, Elfeky, Reem, El-Ghoneimy, Dalia Helmy, Fadoo, Zehra, Greenwood, Tatiana, Gustafsson, Britt, Hagelberg, Stefan, Hasle, Henrik, Hästbacka, Johanna, Jadrešin, Oleg, Jädersten, Martin, Kaya, Zuhre, Lecumberri, Ranon, Marques, Laura, Mushtaq, Naureen, Naqvi, Ahmed, Neves, João Farela, Nunes, Susana, Paucar, Martin, Payne, Jeanette H., Rascon, Jelena, Ruuska, Terhi Susanna, Saribeyoglu, Ebru Tugrul, Sundin, Mikael C., Svedenkrans, Jenny, Świderska, Natalia, Tedgård, Ulf, Tvedt, Tor Henrik, Ünüvar, Ayşegül, Van Laar, Jan A. M., Weitzman, Sheila, Winiarski, Jacek, Yaseen, Muhamma Zohaib, Yildiz, Mehmet, Zantomio, Daniela, Øra, Ingrid, Øverland, Torstein, Chiang, Samuel C. C., Covill, Laura E., Tesi, Bianca, Campbell, Tessa M., Schlums, Heinrich, Nejati-Zendegani, Jelve, Mördrup, Karina, Wood, Stephanie, Theorell, Jakob, Sekine, Takuya, Al-Herz, Waleed, Akar, Himmet Haluk, Belen, Fatma Burcu, Chan, Mei Yoke, Devecioglu, Omer, Aksu, Tekin, Ifversen, Marianne, Malinowska, Iwona, Sabel, Magnus, Unal, Ekrem, Unal, Sule, Introne, Wendy J., Krzewski, Konrad, Gilmour, Kimberly C., Ehl, Stephan, Ljunggren, Hans-Gustaf, Nordenskjöld, Magnus, Horne, AnnaCarin, Henter, Jan-Inge, Meeths, Marie, and Bryceson, Yenan T.

Published
2024
Full Text
View/download PDF

5. Dendritic cells expressing immunoreceptor CD300f are critical for controlling chronic gut inflammation

Author

Lee, Ha-Na, Tian, Linjie, Bouladoux, Nicolas, Davis, Jacquice, Quinones, Mariam, Belkaid, Yasmine, Coligan, John E., and Krzewski, Konrad

Subjects
Inflammatory bowel diseases -- Genetic aspects -- Models -- Research, Dendritic cells -- Research, Gene expression -- Research, Health care industry
Abstract

Proinflammatory cytokine overproduction and excessive cell death, coupled with impaired clearance of apoptotic cells, have been implicated as causes of failure to resolve gut inflammation in inflammatory bowel diseases. Here we have found that dendritic cells expressing the apoptotic cell-recognizing receptor CD300f play a crucial role in regulating gut inflammatory responses in a murine model of colonic inflammation. CD300f-deficient mice failed to resolve dextran sulfate sodium-induced colonic inflammation as a result of defects in dendritic cell function that were associated with abnormal accumulation of apoptotic cells in the gut. CD300f-deficient dendritic cells displayed hyperactive phagocytosis of apoptotic cells, which stimulated excessive TNF-[alpha] secretion predominantly from dendritic cells. This, in turn, induced secondary IFN-[gamma] overproduction by colonic T cells, leading to prolonged gut inflammation. Our data highlight a previously unappreciated role for dendritic cells in controlling gut homeostasis and show that CD300f-dependent regulation of apoptotic cell uptake is essential for suppressing overactive dendritic cell-mediated inflammatory responses, thereby controlling the development of chronic gut inflammation., Introduction Inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, are chronic relapsing inflammatory disorders within the intestinal lumen arising from a combination of immunological, environmental, and genetic factors [...]

Published
2017
Full Text
View/download PDF

14. Diagnosis of Chediak Higashi disease in a 67‐year old woman

Author

Yarnell, David S., primary, Roney, Joseph C., additional, Teixeira, Cláudia, additional, Freitas, Maria I., additional, Cipriano, Ana, additional, Leuschner, Pedro, additional, Krzewski, Konrad, additional, Stephen, Joshi, additional, Dorward, Heidi, additional, Gahl, William A., additional, Gochuico, Bernadette R., additional, Toro, Camilo, additional, Malicdan, May C., additional, and Introne, Wendy J., additional

Published
2020
Full Text
View/download PDF

15. NK cell defects in X-linked pigmentary reticulate disorder

Author

Starokadomskyy, Petro, primary, Wilton, Katelynn M., additional, Krzewski, Konrad, additional, Lopez, Adam, additional, Sifuentes-Dominguez, Luis, additional, Overlee, Brittany, additional, Chen, Qing, additional, Ray, Ann, additional, Gil-Krzewska, Aleksandra, additional, Peterson, Mary, additional, Kinch, Lisa N., additional, Rohena, Luis, additional, Grunebaum, Eyal, additional, Zinn, Andrew R., additional, Grishin, Nick V., additional, Billadeau, Daniel D., additional, and Burstein, Ezra, additional

Published
2019
Full Text
View/download PDF

17. An actin cytoskeletal barrier inhibits lytic granule release from Natural Killer cells in Chediak-Higashi syndrome

Author

Gil-Krzewska, Aleksandra, Saeed, Mezida B, Oszmiana, Anna, Fischer, E, Lagrue, Kathryn, Gahl, William A, Introne, Wendy J, Coligan, John E, Davis, Daniel M, and Krzewski, Konrad

Abstract

BackgroundChediak-Higashi syndrome (CHS) is a rare disorder caused by biallelic mutations in the LYST gene, resulting in formation of giant lysosomes or lysosome-related organelles in several cell types. The disease is characterized by immunodeficiency and a fatal hemophagocytic lymphohistiocytosis due to impaired function of cytotoxic lymphocytes, mainly Natural Killer (NK) cells.ObjectiveWe sought to determine the underlying biochemical cause of the impaired cytotoxicity of NK cells in CHS.MethodsWe generated a human cell model of CHS, using CRISPR technology. We used a combination of classical techniques to evaluate lysosomal function and cell activity in the model system, and super-resolution microscopy to visualize filamentous (F-)actin and lytic granules in normal and LYST-deficient NK cells.ResultsLoss of LYST function in a human NK cell line, NK92mi, resulted in inhibition of NK cell cytotoxicity and reproduced other aspects of CHS cellular phenotype, including the presence of significantly enlarged lytic granules with defective exocytosis, and impaired integrity of endo-lysosomal compartments. The large granules had an acidic pH, normal activity of lysosomal enzymes, and were positive for the proteins essential for lytic granule exocytosis. Visualization of the actin meshwork openings at the immunological synapse revealed that the cortical actin acts as a barrier for secretion of such large granules at the cell-cell contact site. Decreasing the cortical actin density at the immunological synapse, or decreasing the lytic granule size, restored the ability of LYST-deficient NK cells to degranulate and kill target cells.ConclusionThe cortical actin and granule size play significant roles in NK cell cytotoxic function. The periodicity of sub-synaptic actin is an important factor limiting the release of large lytic granules from CHS NK cells, and could be a novel target for pharmaceutical intervention.

Published
2017

20. Lipopolysaccharide-induced binding of receptor CD300b to Toll-like receptor 4 alters signaling to drive lethal cytokine responses that enhance septic shock

Author

Voss, Oliver H., Murakami, Yousuke, Pena, Mirna Y., Lee, Ha-Na, Tian, Linjie, Margulies, David H., Street, Jonathan M., Yuen, Peter S. T., Qi, Chen-Feng, Krzewski, Konrad, and Coligan, John E.

Subjects
Lipopolysaccharides, Mice, Knockout, Macrophages, NF-kappa B, Peritonitis, Article, Interleukin-10, Mice, Inbred C57BL, Toll-Like Receptor 4, Adaptor Proteins, Vesicular Transport, Mice, Phosphatidylinositol 3-Kinases, HEK293 Cells, Sepsis, Myeloid Differentiation Factor 88, Animals, Humans, Syk Kinase, Receptors, Immunologic, Protein Binding, Signal Transduction
Abstract

Receptor CD300b is implicated in regulating the immune response to bacterial infection by an unknown mechanism. Here, we identified CD300b as a lipopolysaccharide (LPS)-binding receptor and determined the mechanism underlying CD300b augmentation of septic shock. In vivo depletion and adoptive transfer studies identified CD300b-expressing macrophages as the key cell type augmenting sepsis. We showed that CD300b, and its adaptor DAP12, associated with Toll-like receptor 4 (TLR4) upon LPS binding, thereby enhancing TLR4-adaptor MyD88- and TRIF-dependent signaling that resulted in an elevated pro-inflammatory cytokine storm. LPS engagement of the CD300b-TLR4 complex led to the recruitment and activation of spleen tyrosine kinase (Syk) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). This resulted in an inhibition of the ERK1/2 protein kinase- and NF-κB transcription factor-mediated signaling pathways, which subsequently led to a reduced interleukin-10 (IL-10) production. Collectively, our data describe a mechanism of TLR4 signaling regulated by CD300b in myeloid cells in response to LPS.

Published
2016

23. Differences in Granule Morphology yet Equally Impaired Exocytosis among Cytotoxic T Cells and NK Cells from Chediak–Higashi Syndrome Patients

Author

Chiang, Samuel C. C., primary, Wood, Stephanie M., additional, Tesi, Bianca, additional, Akar, Himmet Haluk, additional, Al-Herz, Waleed, additional, Ammann, Sandra, additional, Belen, Fatma Burcu, additional, Caliskan, Umran, additional, Kaya, Zühre, additional, Lehmberg, Kai, additional, Patiroglu, Turkan, additional, Tokgoz, Huseyin, additional, Ünüvar, Ayşegül, additional, Introne, Wendy J., additional, Henter, Jan-Inge, additional, Nordenskjöld, Magnus, additional, Ljunggren, Hans-Gustaf, additional, Meeths, Marie, additional, Ehl, Stephan, additional, Krzewski, Konrad, additional, and Bryceson, Yenan T., additional

Published
2017
Full Text
View/download PDF

24. Efficacy of T cell assays for the diagnosis of primary defects in cytotoxic lymphocyte exocytosis

Author

Chiang, Samuel C.C., Covill, Laura E., Tesi, Bianca, Campbell, Tessa M, Schlums, Heinrich, Nejati-Zendegani, Jelve, Mördrup, Karina, Wood, Stephanie, Theorell, Jakob, Sekine, Takuya, Al-Herz, Waleed, Akar, Himmet Haluk, Belen, Fatma Burcu, Chan, Mei Yoke, Devecioglu, Omer, Aksu, Tekin, Ifversen, Marianne, Malinowska, Iwona, Sabel, Magnus, Unal, Ekrem, Unal, Sule, Introne, Wendy J., Krzewski, Konrad, Gilmour, Kimberly C., Ehl, Stephan, Abboud, Miguel R, Aytac, Sevkiye Selin, Bosse, Franziskus Johannes, Choo, Sharon, Drabko, Katarzyna, Onkologii, Klinika, Elfeky, Reem, El-Ghoneimy, Dalia Helmy, Fadoo, Zehra, Greenwood, Tatiana, Gustafsson, Britt, Hagelberg, Stefan, Hasle, Henrik, Hästbacka, Johanna, Jadrešin, Oleg, Jädersten, Martin, Kaya, Zuhre, Lecumberri, Ranon, Marques, Laura, Mushtaq, Naureen, Naqvi, Ahmed, Neves, João Farela, Nunes, Susana, Paucar, Martin, Payne, Jeanette H., Rascon, Jelena, Ruuska, Terhi Susanna, Saribeyoglu, Ebru Tugrul, Sundin, Mikael C., Svedenkrans, Jenny, Świderska, Natalia, Tedgård, Ulf, Tvedt, Tor Henrik, Ünüvar, Ayşegül, Van Laar, Jan A.M., Weitzman, Sheila, Winiarski, Jacek, Yaseen, Muhamma Zohaib, Yldiz, Mehmet, Zantomio, Daniela, Øra, Ingrid, Øverland, Torstein, Ljunggren, Hans-Gustaf, Nordenskjöld, Magnus, Horne, AnnaCarin, Henter, Jan-Inge, Meeths, Marie, and Bryceson, Yenan T.

Abstract

1.TCR-triggered T cell and FcR-triggered NK-cell exocytosis assays are most accurate for diagnosing defective cytotoxic lymphocyte exocytosis.2.The standard K562 cell assay has high inter-individual variability, is affected by expanded NK-cell subsets and transportation stress.

Published
2024
Full Text
View/download PDF

25. Natural killer cell activity and dysfunction in Hermansky-Pudlak syndrome

Author

Gil-Krzewska, Aleksandra, primary, Murakami, Yousuke, additional, Peruzzi, Giovanna, additional, O'Brien, Kevin J., additional, Merideth, Melissa A., additional, Cullinane, Andrew R., additional, Gahl, William A., additional, Coligan, John E., additional, Gochuico, Bernadette R., additional, and Krzewski, Konrad, additional

Published
2016
Full Text
View/download PDF

27. Lipopolysaccharide-Induced CD300b Receptor Binding to Toll-like Receptor 4 Alters Signaling to Drive Cytokine Responses that Enhance Septic Shock

Author

Voss, Oliver H., primary, Murakami, Yousuke, additional, Pena, Mirna Y., additional, Lee, Ha-Na, additional, Tian, Linjie, additional, Margulies, David H., additional, Street, Jonathan M., additional, Yuen, Peter S.T., additional, Qi, Chen-Feng, additional, Krzewski, Konrad, additional, and Coligan, John E., additional

Published
2016
Full Text
View/download PDF

28. DNA polymerase-α regulates the activation of type I interferons through cytosolic RNA:DNA synthesis

Author

Starokadomskyy, Petro, primary, Gemelli, Terry, additional, Rios, Jonathan J, additional, Xing, Chao, additional, Wang, Richard C, additional, Li, Haiying, additional, Pokatayev, Vladislav, additional, Dozmorov, Igor, additional, Khan, Shaheen, additional, Miyata, Naoteru, additional, Fraile, Guadalupe, additional, Raj, Prithvi, additional, Xu, Zhe, additional, Xu, Zigang, additional, Ma, Lin, additional, Lin, Zhimiao, additional, Wang, Huijun, additional, Yang, Yong, additional, Ben-Amitai, Dan, additional, Orenstein, Naama, additional, Mussaffi, Huda, additional, Baselga, Eulalia, additional, Tadini, Gianluca, additional, Grunebaum, Eyal, additional, Sarajlija, Adrijan, additional, Krzewski, Konrad, additional, Wakeland, Edward K, additional, Yan, Nan, additional, de la Morena, Maria Teresa, additional, Zinn, Andrew R, additional, and Burstein, Ezra, additional

Published
2016
Full Text
View/download PDF

29. Membrane-Type 6 Matrix Metalloproteinase, MT6-MMP, Regulates the Activation-Induced Down-Modulation of CD16 in Human Primary NK Cells

Author

Peruzzi, Giovanna, Femnou, Laurette, Gil-Krzewska, Aleksandra, Borrego, Francisco, Weck, Jennifer, Krzewski, Konrad, and Coligan, John E.

Subjects
Immunological Synapses, Matrix Metalloproteinases, Membrane-Associated, Transcription, Genetic, Recombinant Fusion Proteins, Down-Regulation, chemical and pharmacologic phenomena, Cell Communication, GPI-Linked Proteins, Lymphocyte Activation, Article, Cell Line, Tumor, Humans, RNA, Small Interfering, Cells, Cultured, Interleukin-15, Cell Membrane, Receptors, IgG, Antibody-Dependent Cell Cytotoxicity, virus diseases, Cell Polarity, hemic and immune systems, Dipeptides, Endocytosis, Cell Compartmentation, Killer Cells, Natural, Protein Transport, Gene Expression Regulation, Interleukin-2, Tetradecanoylphorbol Acetate, RNA Interference
Abstract

CD16 (Fc RIIIa), the low affinity receptor for IgG, expressed by the majority of human natural killer (NK) cells, is a potent activating receptor that facilitates antibody-dependent cell-mediated cytotoxicity (ADCC). ADCC dysfunction has been linked to cancer progression and poor prognosis for chronic infections, such as HIV; thus, understanding how CD16 expression is regulated by NK cells has clinical relevance. Importantly, CD16 cell-surface expression is down-modulated following NK cell activation and, in particular, exposure to stimulatory cytokines (IL-2 or IL-15), likely due to the action of matrix metalloproteinases (MMPs). Here, we identify membrane-type 6 matrix metalloproteinase (MT6, also known as MMP25) as a proteinase responsible for CD16 down-modulation. IL-2-induced up-regulation of MT6/MMP25 cell surface expression correlates with CD16 down-modulation. MT6/MMP25, sequestered in intracellular compartments in unstimulated NK cells, translocates to the cell surface after stimulation; moreover it polarizes to the effector-target cell interface of the CD16-mediated immunological synapse. siRNA-mediated disruption of MT6/MMP25 expression enhances the ADCC capacity of NK cells, emphasizing the important functional role of MT6/MMP25 in the regulation of ADCC activity. Thus, this study uncovers a previously unknown role of MT6/MMP25 in human NK cells, and suggests that inhibition of MT6/MMP25 activity could improve ADCC efficacy of therapeutically administered NK cells that require IL-2 for culture and expansion.

Published
2013

30. Toso, a functional IgM receptor, is regulated by IL-2 in T and NK cells1

Author

Murakami, Yousuke, Narayanan, Sriram, Su, Su, Childs, Richard, Krzewski, Konrad, Borrego, Francisco, Weck, Jennifer, and Coligan, John E.

Subjects
Killer Cells, Natural, Jurkat Cells, HEK293 Cells, T-Lymphocyte Subsets, Humans, Interleukin-2, Membrane Proteins, Apoptosis, Receptors, Fc, fas Receptor, Apoptosis Regulatory Proteins, Article, Signal Transduction
Abstract

We find that the cell surface receptor Toso is dramatically downregulated by in vitro stimulation of human T and NK cells with IL-2 in a STAT5-dependent manner. The fact that IL-2 is known to prime NK and T cells for Fas/TNF-mediated activation-induced cell death (AICD) fits nicely with the original and recent descriptions of Toso as an inhibitor of Fas/TNF-induced apoptosis. In support of this possibility, effector memory T cells express markedly lower levels of Toso than those of naive T cells, indicating that activation in vivo correlates with the downregulation of Toso. Moreover, in vitro activation of memory T cells through TCR dramatically downregulates Toso expression compared with that of naive CD4 T cells. However, overexpression of Toso in human NK cells and Jurkat T cells does not inhibit Fas-mediated apoptosis, and, in agreement with other recent reports, Toso clearly functions as an IgM receptor. Unlike CD16, Toso expression by NK cells does not convey cytotoxic potential, but its ligation does trigger intracellular signaling in NK cells. In summary, our data indicate that Toso is a functional IgM receptor that is capable of activating signaling molecules, is regulated by IL-2, and is not inherently an antiapoptotic molecule.

Published
2012

32. Natural killer cell activity and dysfunction in Hermansky-Pudlak syndrome.

Author

Gil‐Krzewska, Aleksandra, Murakami, Yousuke, Peruzzi, Giovanna, O'Brien, Kevin J., Merideth, Melissa A., Cullinane, Andrew R., Gahl, William A., Coligan, John E., Gochuico, Bernadette R., and Krzewski, Konrad

Subjects
KILLER cells, HERMANSKY-Pudlak syndrome, HUMAN chromosome abnormalities, LYSOSOMES, ORGANELLES, IMMUNODEFICIENCY
Abstract

Hermansky-Pudlak syndrome ( HPS) encompasses disorders with abnormal function of lysosomes and lysosome-related organelles, and some patients who develop immunodeficiency. The basic mechanisms contributing to immune dysfunction in HPS are ill-defined. We analysed natural killer ( NK) cells from patients diagnosed with HPS-1, HPS-2, HPS-4, and an unreported HPS subtype. NK cells from an HPS-2 and an unreported HPS subtype share a similar cellular phenotype with defective granule release and cytotoxicity, but differ in cytokine exocytosis. Defining NK cell activity in several types of HPS provides insights into cellular defects of the disorder and understanding of mechanisms contributing to HPS pathogenesis. [ABSTRACT FROM AUTHOR]

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results