Intestinal microbiota link lymphopenia to murine autoimmunity via PD-1+CXCR5−/dim B-helper T cell induction View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-04-26

AUTHORS

Toshiki Eri, Kimito Kawahata, Takeyuki Kanzaki, Mitsuru Imamura, Kazuya Michishita, Lisa Akahira, Ei Bannai, Noritada Yoshikawa, Yasumasa Kimura, Takeshi Satoh, Satoshi Uematsu, Hirotoshi Tanaka, Kazuhiko Yamamoto

ABSTRACT

T cell lymphopenia results in peripheral homeostatic expansion to maintain the T cell immune system, which is termed lymphopenia-induced proliferation (LIP). LIP is a potential risk for expanding autoreactive clones to become pathogenic in human and murine autoimmune diseases. However, the ontogeny of T cells that induce autoantibody production by autoreactive B cells in LIP remains unclear. Transfer of CD4+CD25- conventional T (Tc) cells into T-cell-deficient athymic nude mice has been previously reported as a LIP-induced autoimmune model which develops organ-specific autoimmune diseases and systemic antinuclear antibodies (ANAs). We show here that via LIP in this model, Tc cells proliferated and differentiated into PD-1+CXCR5-/dim B-helper T cells, which promoted splenic germinal center (GC) formation, provided help for autoantibody-producing B cells, and had distinctive features of follicular helper T (Tfh) cells except that they do not express high CXCR5. Intestinal microbiota were essential for their generation, since depletion of them in recipient mice by antibiotics resulted in a reduction of LIP-induced PD-1+CXCR5-/dim B-helper T cells and an amelioration of autoimmune responses. Our findings will contribute to the elucidation of the mechanism of lymphopenia-induced autoimmunity and autoantibody production, and will pave the way for microbiota-targeted novel therapeutic approaches to systemic autoimmune diseases. More... »

PAGES

46037

Journal

TITLE

Scientific Reports

ISSUE

1

VOLUME

7

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep46037

DOI

http://dx.doi.org/10.1038/srep46037

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1084955216

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28443628


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