Publication Date:
2011-07-19
Description:
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. 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), the mouse model for multiple sclerosis. The factors that are needed for the generation of T(H)17 cells have been well characterized. 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148838/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148838/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Esplugues, Enric -- Huber, Samuel -- Gagliani, Nicola -- Hauser, Anja E -- Town, Terrence -- Wan, Yisong Y -- O'Connor, William Jr -- 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 -- DK45735/DK/NIDDK NIH HHS/ -- P30 DK045735/DK/NIDDK NIH HHS/ -- P30 DK045735-20/DK/NIDDK NIH HHS/ -- R01 HL061271/HL/NHLBI NIH HHS/ -- R01 HL062052/HL/NHLBI NIH HHS/ -- R21 HL104601/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Jul 17;475(7357):514-8. doi: 10.1038/nature10228.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. enric.esplugues@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21765430" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antibodies/immunology/pharmacology
;
Antigens, CD3/immunology
;
CD4-Positive T-Lymphocytes/immunology/transplantation
;
Cell Movement/drug effects
;
Chemokine CCL20/immunology
;
Disease Models, Animal
;
Encephalomyelitis, Autoimmune, Experimental/immunology
;
Female
;
Gene Expression Profiling
;
Gene Expression Regulation/immunology
;
Influenza A virus/immunology
;
Interleukin-17/immunology
;
Intestine, Small/cytology/*immunology
;
Male
;
Mice
;
Mice, Inbred BALB C
;
Mice, Inbred C57BL
;
Mice, Transgenic
;
Orthomyxoviridae Infections/immunology
;
Receptors, CCR6/immunology
;
Sepsis/immunology
;
Staphylococcal Infections/immunology
;
Th17 Cells/*immunology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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