Focused specificity of intestinal TH17 cells towards commensal bacterial antigens

Yi Yang, Miriam B. Torchinsky, Michael Gobert, Huizhong Xiong, Mo Xu, Jonathan L. Linehan, Francis Alonzo, Charles Ng, Alessandra Chen, Xiyao Lin, Andrew Sczesnak, Jia Jun Liao, Victor J. Torres, Marc Jenkins, Juan J. Lafaille, Dan R. Littman

Research output: Contribution to journalArticlepeer-review

275 Scopus citations

Abstract

T-helper-17 (TH17) cells have critical roles in mucosal defence and in autoimmune disease pathogenesis. They are most abundant in the small intestine lamina propria, where their presence requires colonization of mice with microbiota. Segmented filamentous bacteria (SFB) are sufficient to induce TH17 cells and to promote TH17-dependent autoimmune disease in animal models. However, the specificity of TH17 cells, the mechanism of their induction by distinct bacteria, and the means by which they foster tissue-specific inflammation remain unknown. Here we show that the T-cell antigen receptor (TCR) repertoire of intestinal TH17 cells in SFB-colonized mice has minimal overlap with that of other intestinal CD4 + T cells and that most TH17 cells, but not other T cells, recognize antigens encoded by SFB. T cells with antigen receptors specific for SFB-encoded peptides differentiated into RORÎ 3t-expressing TH17 cells, even if SFB-colonized mice also harboured a strong T H 1 cell inducer, Listeria monocytogenes, in their intestine. The match of T-cell effector function with antigen specificity is thus determined by the type of bacteria that produce the antigen. These findings have significant implications for understanding how commensal microbiota contribute to organ-specific autoimmunity and for developing novel mucosal vaccines.

Original languageEnglish (US)
Pages (from-to)152-156
Number of pages5
JournalNature
Volume510
Issue number7503
DOIs
StatePublished - 2014

Bibliographical note

Funding Information:
Acknowledgements We thank S. Yong Kim for generating TCR transgenic mice, A. Viale for 454 pyrosequencing, R. Myers for RNA-seq, N. Freitag for providing the Listeria strain and expression vector, Y. Umesaki for SFB samples, and K. Murphy for providing the 58a2b2 hybridoma line. The Immune Monitoring Core New York University (NYU) is supported in part by grant UL1 TR00038 from the National Center for Advancing Translational Sciences and grant 5P30CA016087-32 from the National Cancer Institute; the NYU Histology Core is supported in part by grant 5P30CA016087-32 from the National Cancer Institute. M.K.J. was supported by grant R01 AI039614 from the NIH. Y.Y. was supported by the Arthritis National Research Foundation. M.X. is supported by the Irvington Institute fellowship program of the Cancer Research Institute. D.R.L. is a Howard Hughes Medical Institute Investigator.

Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.

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