title: T follicular helper cells mediate expansion of regulatory B cells via IL-21 in Lupus-prone MRL/lpr mice.
abstract: T follicular helper (Tfh) cells can mediate humoral immune responses and augment autoimmunity, whereas the role of Tfh cells on regulatory B (B10) cells in autoimmunity diseases is not clear. Here, we investigated the percentages of Tfh cells and B10 cells in lupus-prone MRL/Mp-lpr/lpr (MRL/lpr) mice and examined the effects and mechanism of Tfh cell-derived interleukin-21 (IL-21) on IL-10 production during the differentiation of B10 cells. Both Tfh cells and B10 cells were expanded in spleens of MRL/lpr mice. In addition, a positive correlation between the proportions of Tfh cells and B10 cells was observed. Tfh cell-derived IL-21 from MRL/lpr mice could promote IL-10 production during the differentiation of B10 cells. Importantly, neutralization of IL-21 inhibited IL-10 production and expansion of B10 cells both in vitro and in vivo. IL-21 induced IL-10 production via activation of phosphorylated signal transduction and activator of transcription 3 (p-STAT3). Inhibition of p-STAT3 effectively blocked IL-10 production during the differentiation of B10 cells. Moreover, IL-21-induced IL-10 exerted a regulatory function by inhibiting the proliferation of T cells. These data suggest that Tfh cells not only mediate humoral immune responses and augment autoimmunity but also play a broader role in immune regulatory actions via the induction of IL-10 production.
authors: Division of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China.
authors: Xue
authors: X
authors: Yang
authors: Ji
authors: J
authors: Yang
authors: Yiwei
authors: Y
authors: Chu
authors: Jiucun
authors: J
authors: Wang
authors: Ming
authors: M
authors: Guan
authors: Xiaoxia
authors: X
authors: Zhu
authors: Yu
authors: Y
authors: Xue
authors: Hejian
authors: H
authors: Zou
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity; D060151:B-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D016753:Interleukin-10 / Q000096:biosynthesis; D007378:Interleukins / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D050796:STAT3 Transcription Factor / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism*; D000098546:Interleukin-21
chemical_list: D001323:Autoantibodies; D007378:Interleukins; D050796:STAT3 Transcription Factor; D016753:Interleukin-10; D000098546:Interleukin-21
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