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Intestinal microbiota link lymphopenia to murine autoimmunity via PD-1+CXCR5-/dim B-helper T cell induction.
Eri, Toshiki; Kawahata, Kimito; Kanzaki, Takeyuki; Imamura, Mitsuru; Michishita, Kazuya; Akahira, Lisa; Bannai, Ei; Yoshikawa, Noritada; Kimura, Yasumasa; Satoh, Takeshi; Uematsu, Satoshi; Tanaka, Hirotoshi; Yamamoto, Kazuhiko.
Afiliação
  • Eri T; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Kawahata K; Department of Rheumatology and Allergy, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Kanzaki T; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Imamura M; Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
  • Michishita K; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Akahira L; Department of Internal Medicine, Yamanashi Prefectural Central Hospital, Yamanashi, Japan.
  • Bannai E; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Yoshikawa N; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Kimura Y; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Satoh T; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Uematsu S; Department of Rheumatology and Allergy, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Tanaka H; Division of Systems Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Yamamoto K; Division of Systems Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Sci Rep ; 7: 46037, 2017 04 26.
Article em En | MEDLINE | ID: mdl-28443628
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos B / Autoimunidade / Linfócitos T Auxiliares-Indutores / Receptores CXCR5 / Receptor de Morte Celular Programada 1 / Microbioma Gastrointestinal / Linfopenia Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Sci Rep Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos B / Autoimunidade / Linfócitos T Auxiliares-Indutores / Receptores CXCR5 / Receptor de Morte Celular Programada 1 / Microbioma Gastrointestinal / Linfopenia Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Sci Rep Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Japão