Control of TH17 cells occurs in the Small Intestine

By E. Esplugues, S. Huber, N. Gagliani, A. Hauser, T. Town, Y. Wan, William O'Connor, A. Rongvaux, N. Van Rooijen, A. Haberman and 6 more. Nature, 2011

679 citations recorded by the source corpus.

Interleukin (IL)-17-producing T helper cells (TH17) are a recently identified CD4+ T cell subset distinct from T helper type 1 (TH1) and T helper type 2 (TH2) cells. TH17 cells can drive antigen-specific autoimmune diseases and are considered the main population of pathogenic T cells driving experimental autoimmune encephalomyelitis (EAE), the mouse model for multiple sclerosis. The factors that are needed for the generation of TH17 cells have been well characterized. However, where and how the immune system controls TH17 cells in vivo remains unclear. Here, by using a model of tolerance induced by CD3-specific antibody, a model of sepsis and influenza A viral infection (H1N1), we show that pro-inflammatory TH17 cells can be redirected to and controlled in the small intestine. TH17-specific IL-17A secretion induced expression of the chemokine CCL20 in the small intestine, facilitating the migration of these cells specifically to the small intestine via the CCR6/CCL20 axis. Moreover, we found that TH17 cells are controlled by two different mechanisms in the small intestine: first, they are eliminated via the intestinal lumen; second, pro-inflammatory TH17 cells simultaneously acquire a regulatory phenotype with in vitro and in vivo immune-suppressive properties (rTH17). These results identify mechanisms limiting TH17 cell pathogenicity and implicate the gastrointestinal tract as a site for control of TH17 cells.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/fdf73f6fd9c7187fb3971c53bd4223c82c4b35c3

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In Immunology

Citations in the corpus

The Microbiome in Infectious Disease and Inflammation (2012, neutral): “Interestingly, proinflammatory Th17 cells can be redirected to and controlled in the small intestine (169).”
Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine. (2015, neutral): “Despite its limitations, especially in the context of CNS autoimmunity, the ability of anti-CD3 to induce acute immune activation offers a valuable setup to shed further light on the distribution of auto-antigen-specific Th cells under an LA-rich diet (Esplugues et al., 2011).”
Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation (2015, background): “LETTER doi:10.1038/nature14452 TH17 cells transdifferentiate into regulatory T cells during resolution of inflammation Nicola Gagliani1, Maria Carolina Amezcua Vesely1*, Andrea Iseppon1*, Leonie Brockmann2, Hao Xu1, Noah W. Palm1, Marcel R. de Zoete1,3, Paula Licona-Limón1{, Ricardo S. Paiva1, Trav”
Th17 cells: biology, pathogenesis of autoimmune and inflammatory diseases, and therapeutic strategies. (2012, background): “inflammatory conditions in the gastrointestinal tract, Th17 cells can also acquire regulatory phenotype with immunosuppressive functions.(58) At molecular level, Th17 plasticity has been”
The Chemokine Superfamily Revisited (2012, neutral): “These divergent results may be explained by the fact that mouse Ccl8 is actually not the counterpart of human CCL8 but is instead a mouse-specific chemokine like mouse Ccl12 (Table 1).”
Single-cell Genomics Unveils Critical Regulators of Th17 cell Pathogenicity (2015, neutral): “Finally, a population based signature comparing profiles of EAE Th17 cells to lamina propria lymphocyte (LPL) Th17 cells (Supplemental Experimental Procedures, Figure S3), which are known to assume a regulatory phenotype (Esplugues et al., 2011; O'Connor et al., 2009), correlates with PC1 in vivo (p”