%0 Journal Article
%T IL-10-producing regulatory B cells restrain the T follicular helper cell response in primary Sj£¿gren¡¯s syndrome
%J -
%D 2019
%R https://doi.org/10.1038/s41423-019-0227-z
%X Increased numbers of T follicular helper (Tfh) cells have been implicated in the development of autoimmune diseases including primary Sj£¿gren¡¯s syndrome (pSS), but how the Tfh cell response is regulated during autoimmune pathogenesis remains largely unclear. Here, we first found negative correlations between IL-10+ regulatory B (Breg) cell numbers and Tfh cell responses and disease activity in patients with pSS and mice with experimental Sj£¿gren¡¯s syndrome (ESS). Moreover, we detected high expression of IL-10 receptor on Tfh cells and their precursors in both humans and mice. In culture, IL-10 suppressed human and murine Tfh cell differentiation by promoting STAT5 phosphorylation. By using an adoptive transfer approach and two-photon live imaging, we found significantly increased numbers of Tfh cells with enhanced T cell homing into B cell follicles in the draining cervical lymph nodes of RAG-2£¿/£¿ mice transferred with IL-10-deficient B cells during ESS development compared with those of RAG-2£¿/£¿ mice transferred with wild-type B cells. In ESS mice, CD19+CD1dhiCD5+ Breg cells with decreased IL-10 production exhibited severely impaired suppressive effects on T cell proliferation. Consistently, CD19+CD24+CD38hi Breg cells from pSS patients showed significantly reduced IL-10 production with defective inhibitory function in the suppression of autologous Tfh cell expansion. Furthermore, the adoptive transfer of IL-10-producing Breg cells markedly suppressed the Tfh cell response and ameliorated ESS progression in ESS mice. Together, these findings demonstrate a critical role for IL-10-producing Breg cells in restraining the effector Tfh cell response during pSS development
%U https://www.nature.com/articles/s41423-019-0227-z