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Ligation of CD180 inhibits IFN-α signaling in a Lyn-PI3K-BTK-dependent manner in B cells

Cellular & Molecular Immunology volume 14, pages 192–202 (2017)Cite this article

Abstract

A hallmark of systemic lupus erythematosus (SLE) is the consistent production of various auto-antibodies by auto-reactive B cells. Interferon-α (IFN-α) signaling is highly activated in SLE B cells and plays a vital role in the antibody response by B cells. Previous studies have shown that CD180-negative B cells, which are dramatically increased in SLE patients, are responsible for the production of auto-antibodies. However, the association between CD180 and IFN-α signaling remains unknown. In the present study, we explored the effect of CD180 on regulating the activation of IFN-α signaling in B cells. We found that the number of CD180-negative B cells was increased in MRL/Mp-Fas(lpr/lpr) lupus-prone mice compared with wild-type mice. Phenotypic analysis showed that CD180-negative B cells comprised CD138+ plasmablast/plasma cells and GL-7+ germinal center (GC) B cells. Notably, ligation of CD180 significantly inhibited the IFN-α-induced phosphorylation of signal transducer and activator of transcription 2 (STAT-2) and expression of IFN-stimulated genes (ISGs) in a Lyn-PI3K-BTK-dependent manner in vitro. Moreover, ligation of CD180 could also inhibit IFN-α-induced ISG expression in B cells in vivo. Furthermore, the Toll-like receptor 7 and Toll-like receptor 9 signaling pathways could significantly downregulate CD180 expression and modulate the inhibitory effect of CD180 signaling on the activation of IFN-α signaling. Collectively, our results highlight the close association between the increased proportion of CD180-negative B cells and the activation of IFN-α signaling in SLE. Our data provide molecular insight into the mechanism of IFN-α signaling activation in SLE B cells and a potential therapeutic approach for SLE treatment.

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Acknowledgements

This work was supported by a grant from National Natural Science Foundation of China (Project number: 31370899).

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Author notes

  1. Ming You and Guanjun Dong: Both Ming You and Guanjun Dong contributed equally to this work.

  2. Dr. Yayi Hou, The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, China. E-mail: yayihou@nju.edu.cn

Authors and Affiliations

  1. Division of Immunology, The State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University, Nanjing, 210093, People’s Republic of China

    Ming You, Guanjun Dong, Fanlin Li, Feiya Ma, Jing Ren, Yujun Xu, Huimin Yue, Ruijing Tang, Deshan Ren & Yayi Hou

  2. Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, 210093, People’s Republic of China

    Yayi Hou

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You, M., Dong, G., Li, F. et al. Ligation of CD180 inhibits IFN-α signaling in a Lyn-PI3K-BTK-dependent manner in B cells. Cell Mol Immunol 14, 192–202 (2017). https://doi.org/10.1038/cmi.2015.61

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