Gut microbiota regulates K/BxN autoimmune arthritis through follicular helper T but not Th17 cells

Katharine E. Block, Zhong Zheng, Alexander Dent, Barbara L. Kee, Haochu Huang

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The bacterial community that colonizes mucosal surfaces helps shape the development and function of the immune system. The K/BxN autoimmune arthritis model is dependent on the microbiota, and particularly on segmented filamentous bacteria, for the autoimmune phenotype. The mechanisms of how the gut microbiota affects arthritis development are not well understood. In this study, we investigate the contribution of two T cell subsets, Th17 and follicular helper T (Tfh), to arthritis and how microbiota modulates their differentiation. Using genetic approaches, we demonstrate that IL-17 is dispensable for arthritis. Antibiotic treatment inhibits disease in IL-17-deficient animals, suggesting that the gut microbiota regulates arthritis independent of Th17 cells. In contrast, conditional deletion of Bcl6 in T cells blocks Tfh cell differentiation and arthritis development. Furthermore, Tfh cell differentiation is defective in antibiotic-treated mice. Taken together, we conclude that gut microbiota regulates arthritis through Tfh but not Th17 cells. These findings have implications in our understanding of how environmental factors contribute to the development of autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)1550-1557
Number of pages8
JournalJournal of Immunology
Volume196
Issue number4
DOIs
StatePublished - Feb 15 2016

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Th17 Cells
Arthritis
Interleukin-17
Microbiota
Helper-Inducer T-Lymphocytes
Cell Differentiation
Anti-Bacterial Agents
T-Lymphocyte Subsets
Gastrointestinal Microbiome
Autoimmune Diseases
Immune System
Bacteria
T-Lymphocytes
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

Gut microbiota regulates K/BxN autoimmune arthritis through follicular helper T but not Th17 cells. / Block, Katharine E.; Zheng, Zhong; Dent, Alexander; Kee, Barbara L.; Huang, Haochu.

In: Journal of Immunology, Vol. 196, No. 4, 15.02.2016, p. 1550-1557.

Research output: Contribution to journalArticle

Block, Katharine E. ; Zheng, Zhong ; Dent, Alexander ; Kee, Barbara L. ; Huang, Haochu. / Gut microbiota regulates K/BxN autoimmune arthritis through follicular helper T but not Th17 cells. In: Journal of Immunology. 2016 ; Vol. 196, No. 4. pp. 1550-1557.
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