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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<jats:sup>+<\/jats:sup>CD25<jats:sup>\u2212<\/jats:sup>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<jats:sup>+<\/jats:sup>CXCR5<jats:sup>\u2212\/dim<\/jats:sup>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<jats:sup>+<\/jats:sup>CXCR5<jats:sup>\u2212\/dim<\/jats:sup>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.<\/jats:p>","DOI":"10.1038\/srep46037","type":"journal-article","created":{"date-parts":[[2017,4,26]],"date-time":"2017-04-26T09:07:18Z","timestamp":1493197638000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Intestinal microbiota link lymphopenia to murine autoimmunity via PD-1+CXCR5\u2212\/dim B-helper T cell induction"],"prefix":"10.1038","volume":"7","author":[{"given":"Toshiki","family":"Eri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimito","family":"Kawahata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeyuki","family":"Kanzaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Imamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Michishita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Akahira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ei","family":"Bannai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noritada","family":"Yoshikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasumasa","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Satoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Uematsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotoshi","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,4,26]]},"reference":[{"key":"BFsrep46037_CR1","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/S0065-2776(08)60641-0","volume":"44","author":"EM Tan","year":"1989","unstructured":"Tan, E. 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