%0 Journal Article
%T IL-17B alleviates the pathogenesis of systemic lupus erythematosus by inhibiting FASN-mediated differentiation of B cells.
%A Xiao Y
%A Hu Y
%A Gao Y
%A Wang L
%A Zhang L
%A Ma Q
%A Ning Z
%A Yu L
%A Li H
%A Liu J
%A Wang J
%A Yang Y
%A Xiong H
%A Dong G
%J JCI Insight
%V 0
%N 0
%D 2024 Aug 8
%M 39115936
%F 9.484
%R 10.1172/jci.insight.181906
%X The interleukin-17 (IL-17) family of cytokines has emerged as a critical player in autoimmune disease, including systemic lupus erythematosus (SLE). However, the role of IL-17B, a poorly understood cytokine, in the pathogenesis of SLE is still not clear. In this study, we investigated the role of IL-17B in the activation and differentiation of B cells, and the pathogenesis of SLE. Intriguingly, IL-17B deficiency aggravated disease in lupus-prone mice and promoted the activation of B cells and the differentiation of germinal center (GC) B cells and plasma cells, while recombinant mouse IL-17B (rmIL-17B) significantly alleviated disease in lupus-prone mice. Mechanistically, rmIL-17B inhibited the activation of the Toll-like receptor (TLR) and interferon (IFN) pathways in B cells by downregulating the FASN-mediated lipid metabolism. Loss of FASN significantly alleviated the disease in lupus-prone mice and inhibited the activation and differentiation of B cells. In addition, B cells had greater FASN expression and lower IL-17RB levels in patients with SLE than in healthy controls. Our study described the role of IL-17B in regulating B-cell activation and differentiation, and alleviating the onset of SLE. These findings will lay a theoretical foundation for further understanding of the pathogenesis of SLE.