Control of TH17 cells occurs in the small intestine

• Published in: Nature (London) Vol. 475; no. 7357; pp. 514 - 518
• Main Authors: Esplugues, Enric, Huber, Samuel, Gagliani, Nicola, Hauser, Anja E., Town, Terrence, Wan, Yisong Y., O’Connor, William, Rongvaux, Anthony, Van Rooijen, Nico, Haberman, Ann M., Iwakura, Yoichiro, Kuchroo, Vijay K., Kolls, Jay K., Bluestone, Jeffrey A., Herold, Kevan C., Flavell, Richard A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.07.2011; Nature Publishing Group
• Subjects: 631/250/1619/554/1898/1273; 692/420/2780; 692/698/2741/520; 692/699/249/2510; Animals; Antibodies - immunology; Antibodies - pharmacology; Biological and medical sciences; CD3 Complex - immunology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - transplantation; Cell Movement - drug effects; Chemokine CCL20 - immunology; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental - immunology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression Profiling; Gene Expression Regulation - immunology; Genetics of the immune response; Humanities and Social Sciences; Immunobiology; Influenza A virus - immunology; Interleukin-17 - immunology; Intestine, Small - cytology; Intestine, Small - immunology; letter; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; multidisciplinary; Orthomyxoviridae Infections - immunology; Receptors, CCR6 - immunology; Science; Science (multidisciplinary); Sepsis - immunology; Staphylococcal Infections - immunology; Th17 Cells - immunology; Immunopathology; Animal model; TH17 lymphocyte; Vertebrata; Regulation(control); Mammalia; Mouse; Biological model; Rodentia; Autoimmune disease; Small intestine
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature10228

Keeping T H 17 cells under wraps Interleukin-17-producing T helper (T H 17) cells serve an important role in the immune system, but are strongly implicated in the pathogenesis of numerous autoimmune diseases including rheumatoid arthritis and multiple sclerosis. How the immune system controls T H 17 cells in vivo remains unclear. Using mice in which tolerance was induced by CD3-specific antibody, a model of sepsis and influenza A viral infection, Esplugues et al . demonstrate that T H 17 cells are kept in check by redirecting the cells to the small intestine where they are eliminated or re-programmed to acquire immunosuppressive and regulatory properties. This work identifies the gastrointestinal tract as a site for control of T H 17 cells. Interleukin (IL)-17-producing T helper cells (T H 17) are a recently identified CD4 + T cell subset distinct from T helper type 1 (T H 1) and T helper type 2 (T H 2) cells 1 . T H 17 cells can drive antigen-specific autoimmune diseases and are considered the main population of pathogenic T cells driving experimental autoimmune encephalomyelitis (EAE) 2 , the mouse model for multiple sclerosis. The factors that are needed for the generation of T H 17 cells have been well characterized 3 , 4 , 5 , 6 . However, where and how the immune system controls T H 17 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 T H 17 cells can be redirected to and controlled in the small intestine. T H 17-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 T H 17 cells are controlled by two different mechanisms in the small intestine: first, they are eliminated via the intestinal lumen; second, pro-inflammatory T H 17 cells simultaneously acquire a regulatory phenotype with in vitro and in vivo immune-suppressive properties (rT H 17). These results identify mechanisms limiting T H 17 cell pathogenicity and implicate the gastrointestinal tract as a site for control of T H 17 cells.