IL-17B alleviates the pathogenesis of systemic lupus erythematosus by inhibiting FASN-mediated differentiation of B cells
Yucai Xiao, Yuxin Hu, Yangzhe Gao, Lin Wang, Lili Zhang, Qun Ma, Zhaochen Ning, Lu Yu, Haochen Li, Jiakun Liu, Junyu Wang, Yonghong Yang, Huabao Xiong, Guanjun Dong
Yucai Xiao, Yuxin Hu, Yangzhe Gao, Lin Wang, Lili Zhang, Qun Ma, Zhaochen Ning, Lu Yu, Haochen Li, Jiakun Liu, Junyu Wang, Yonghong Yang, Huabao Xiong, Guanjun Dong
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Research Article

IL-17B alleviates the pathogenesis of systemic lupus erythematosus by inhibiting FASN-mediated differentiation of B cells

Abstract

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 known. 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 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 and interferon pathways in B cells by downregulating fatty acid synthase–mediated (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 describes 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.

Authors

Yucai Xiao, Yuxin Hu, Yangzhe Gao, Lin Wang, Lili Zhang, Qun Ma, Zhaochen Ning, Lu Yu, Haochen Li, Jiakun Liu, Junyu Wang, Yonghong Yang, Huabao Xiong, Guanjun Dong

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Figure 2

IL-17B represses B cell activation and differentiation in vivo.

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IL-17B represses B cell activation and differentiation in vivo. (A) Unif...
(A) Uniform Manifold Approximation and Projection plot of spleen cells from IMQ-treated WT (n = 2) and IL-17B–KO mice (n = 2). (B) Proportion of cell types in the splenocytes of IMQ-treated WT (n = 2) or IL-17B–KO mice (n = 2). (C) KEGG analysis of splenic GC B cells from IMQ-treated WT and IL-17B–KO mice. Representative flow cytometry images and statistical analysis of the percentages of (D) splenic GC B cells (B220+GL-7+CD95+), (E) plasma cells (CD138+B220–), and the expression of (F) CD86 and (G) CD69 on B220+ B cells in IMQ-treated WT or IL-17B–KO mice. The percentages of (H) spleen GC B cells, (I) plasma cells, and the expression of (J) CD86 and (K) CD69 on B220+ B cells in IMQ-induced WT mice treated with vehicle or rmIL-17B. The data are shown as the mean ± SEM and are representative of 3 independent experiments. *P < 0.05, **P < 0.01, ***P < 0.001 by 2-tailed Student’s t test. NS, P > 0.05.