Induction and molecular signature of pathogenic TH17 cells
Youjin Lee,Amit Awasthi,Amit Awasthi,Nir Yosef,Nir Yosef,Francisco J. Quintana,Sheng Xiao,Anneli Peters,Chuan Wu,Markus Kleinewietfeld,Sharon R. Kunder,David A. Hafler,Raymond A. Sobel,Aviv Regev,Aviv Regev,Vijay K. Kuchroo +15 more
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TLDR
It is found that the production of TGF-β3 by developing Th17 cells was dependent on IL-23, which together with IL-6 induced very pathogenic TH17 cells, which had a molecular signature that defined pathogenic effector TH 17 cells in autoimmune disease.Abstract:
Interleukin 17 (IL-17)-producing helper T cells (T(H)17 cells) are often present at the sites of tissue inflammation in autoimmune diseases, which has led to the conclusion that T(H)17 cells are main drivers of autoimmune tissue injury. However, not all T(H)17 cells are pathogenic; in fact, T(H)17 cells generated with transforming growth factor-β1 (TGF-β1) and IL-6 produce IL-17 but do not readily induce autoimmune disease without further exposure to IL-23. Here we found that the production of TGF-β3 by developing T(H)17 cells was dependent on IL-23, which together with IL-6 induced very pathogenic T(H)17 cells. Moreover, TGF-β3-induced T(H)17 cells were functionally and molecularly distinct from TGF-β1-induced T(H)17 cells and had a molecular signature that defined pathogenic effector T(H)17 cells in autoimmune disease.read more
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The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide
Sophie Viaud,Sophie Viaud,Fabiana Saccheri,Grégoire Mignot,Takahiro Yamazaki,Romain Daillère,Romain Daillère,Dalil Hannani,David Enot,David Enot,Christina Pfirschke,Camilla Engblom,Mikael J. Pittet,Andreas Schlitzer,Florent Ginhoux,Lionel Apetoh,Elisabeth Chachaty,Paul Louis Woerther,Gérard Eberl,Marion Bérard,Chantal Ecobichon,Chantal Ecobichon,Dominique Clermont,Chantal Bizet,Valérie Gaboriau-Routhiau,Valérie Gaboriau-Routhiau,Nadine Cerf-Bensussan,Nadine Cerf-Bensussan,Paule Opolon,Nadia Yessaad,Eric Vivier,Bernhard Ryffel,Charles O. Elson,Joël Doré,Joël Doré,Guido Kroemer,Patricia Lepage,Patricia Lepage,Ivo G. Boneca,Ivo G. Boneca,François Ghiringhelli,François Ghiringhelli,Laurence Zitvogel,Laurence Zitvogel,Laurence Zitvogel +44 more
TL;DR: It is demonstrated that cyclophosphamide alters the composition of microbiota in the small intestine and induces the translocation of selected species of Gram-positive bacteria into secondary lymphoid organs, which suggests that the gut microbiota help shape the anticancer immune response.
Journal ArticleDOI
The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing
TL;DR: This Review focuses on the recent advances that have been made regarding the transcriptional control of TH 17 cell plasticity and stability, as well as the effector functions of TH17 cells, and highlights the mechanisms of IL-17 signalling in mesenchymal and barrier epithelial tissues.
Journal ArticleDOI
Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis.
Noriko Komatsu,Kazuo Okamoto,Shinichiro Sawa,Tomoki Nakashima,Masatsugu Oh-hora,Tatsuhiko Kodama,Sakae Tanaka,Jeffrey A. Bluestone,Hiroshi Takayanagi +8 more
TL;DR: It is shown that TH17 cells originating from Foxp3+ T cells have a key role in the pathogenesis of autoimmune arthritis.
Journal ArticleDOI
Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells
Nicola Gagliani,Chiara F. Magnani,Samuel Huber,Monica E. Gianolini,Monica E. Gianolini,Mauro Pala,Paula Licona-Limón,Binggege Guo,De'Broski R. Herbert,Alessandro Bulfone,Filippo Trentini,Clelia Di Serio,Rosa Bacchetta,Marco Andreani,Leonie Brockmann,Silvia Gregori,Richard A. Flavell,Maria Grazia Roncarolo +17 more
TL;DR: The coexpression of CD49b and LAG-3 enables the isolation of highly suppressive human Tr 1 cells from in vitro anergized cultures and allows the tracking of Tr1 cells in the peripheral blood of subjects who developed tolerance after allogeneic hematopoietic stem cell transplantation.
Journal ArticleDOI
Dynamic regulatory network controlling Th17 cell differentiation
Nir Yosef,Alex K. Shalek,Jellert T. Gaublomme,Hulin Jin,Youjin Lee,Amit Awasthi,Amit Awasthi,Chuan Wu,Katarzyna Karwacz,Sheng Xiao,Marsela Jorgolli,David Gennert,Rahul Satija,Arvind Shakya,Diana Lu,John J. Trombetta,Meenu R. Pillai,Peter J. Ratcliffe,Mathew L. Coleman,Mark Bix,Dean Tantin,Hongkun Park,Hongkun Park,Vijay K. Kuchroo,Vijay K. Kuchroo,Aviv Regev,Aviv Regev +26 more
TL;DR: This study identifies and validates 39 regulatory factors, embeds them within a comprehensive temporal network and reveals its organizational principles; it also highlights novel drug targets for controlling TH17 cell differentiation.
References
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