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 language | English (US) |
|---|---|
| Pages (from-to) | 1550-1557 |
| Number of pages | 8 |
| Journal | Journal of Immunology |
| Volume | 196 |
| Issue number | 4 |
| DOIs | |
| State | Published - Feb 15 2016 |
| Externally published | Yes |
Bibliographical note
Funding Information:We thank Drs. Diane Mathis and Christophe Benoist for KRN transgenic mice, B6.H-2g7 congenic mice, Ca2/2B6, and Ca2/2NOD mice. We also thank the University of Chicago Flow Cytometry Core Facility.
Publisher Copyright:
Copyright © 2016 by The American Association of Immunologists, Inc.
