Abstract Title:

Dysbiosis contributes to arthritis development via activation of autoreactive T cells in the intestine.

Abstract Source:

Arthritis Rheumatol. 2016 Jun 22. Epub 2016 Jun 22. PMID: 27333153

Abstract Author(s):

Yuichi Maeda, Takashi Kurakawa, Eiji Umemoto, Daisuke Motooka, Yoshinaga Ito, Kazuyoshi Gotoh, Keiji Hirota, Masato Matsushita, Yoki Furuta, Masashi Narazaki, Noriko Sakaguchi, Hisako Kayama, Shota Nakamura, Tetsuya Iida, Yukihiko Saeki, Atsushi Kumanogoh, Shimon Sakaguchi, Kiyoshi Takeda

Article Affiliation:

Yuichi Maeda

Abstract:

OBJECTIVE: The intestinal microbiota is involved in arthritis pathogenesis. Altered microbiota composition has been demonstrated in rheumatoid arthritis (RA) patients. However, it remains unclear how dysbiosis contributes to arthritis development. We investigated whether the altered composition of human intestinal microbiota in RA patients contributes to the development of arthritis.

METHODS: We analyzed fecal microbiota of early RA patients and healthy controls by 16S rRNA-based deep sequencing. We inoculated fecal samples from RA patients and healthy controls into germ-free arthritis-prone SKG mice and evaluated immune responses. We also analyzed whether lymphocytes of SKG mice harboring microbiota from RA patients react with arthritis-related autoantigen, RPL23A.

RESULTS: A subpopulation of early RA patients harbored intestinal microbiota dominated by Prevotella copri; SKG mice harboring microbiota from RA patients contained an increased number of intestinal Th17 cells and developed severe arthritis upon zymosan treatment. Lymphocytes in regional lymph nodes and colon, but not spleen, of these mice showed enhanced IL-17 responses to RPL23A. Naïve SKG T cells, co-cultured with P. copri-stimulated dendritic cells, produced IL-17 in response to RPL23A and rapidly induced arthritis.

CONCLUSIONS: We showed that dysbiosis increases the sensitivity to arthritis via activation of autoreactive T cells in the intestine. Autoreactive SKG T cells are activated by dysbiotic microbiota in the intestine, causing joint inflammation. Dysbiosis is an environmental factor that triggers arthritis development in genetically susceptible mice. This article is protected by copyright. All rights reserved.

Study Type : Animal Study

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