IL-17 sustains the plasma cell response via p38-mediated Bcl-xL RNA stability in lupus pathogenesis


Recent studies have demonstrated a central role for plasma cells in the development of autoimmune diseases, such as systemic lupus erythematosus (SLE). Currently, both the phenotypic features and functional regulation of autoreactive plasma cells during SLE pathogenesis remain largely unclear. In this study, we first found that a major subset of IL-17 receptor-expressing plasma cells potently produced anti-dsDNA IgG upon IL-17A (IL-17) stimulation in SLE patients and lupus mice. Using a humanized lupus mouse model, we showed that the transfer of Th17 cell-depleted PBMCs from lupus patients resulted in a significantly reduced plasma cell response and attenuated renal damage in recipient mice compared to the transfer of total SLE PBMCs. Moreover, long-term BrdU incorporation in lupus mice detected highly enriched long-lived BrdU+ subsets among IL-17 receptor-expressing plasma cells. Lupus mice deficient in IL-17 or IL-17 receptor C (IL-17RC) exhibited a diminished plasma cell response and reduced autoantibody production with attenuated renal damage, while the adoptive transfer of Th17 cells triggered the plasma cell response and renal damage in IL-17-deficient lupus mice. In reconstituted chimeric mice, IL-17RC deficiency resulted in severely impaired plasma cell generation but showed no obvious effect on germinal center B cells. Further mechanistic studies revealed that IL-17 significantly promoted plasma cell survival via p38-mediated Bcl-xL transcript stabilization. Together, our findings identified a novel function of IL-17 in enhancing plasma cell survival for autoantibody production in lupus pathogenesis, which may provide new therapeutic strategies for the treatment of SLE.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.


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This study was funded by grants from the National Natural Science Foundation of China (Nos. 81771761, 91842304, and 81901635), Chongqing International Institute for Immunology (2020YJC10), and Sanming Project of Medicine in Shenzhen (SZSM201512019). We thank Mr. Otis Ko for the technical support and service of the Medical Faculty Core Facility and Laboratory Animal Unit at The University of Hong Kong. We are grateful to Dr. Yoichiro Iwakura (University of Tokyo) for providing Il17a−/− mice.

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K.M.: experimental design and paper writing; W.D., F.X., E. H., Y.T., C.D., L.L. M.H., Y.C., and S.Y.: mouse experiments and paper preparation; N.P., J.L., D.H., Q.H., X.H., X.C., Q.J., and D.L.: clinical data acquisition and analysis; and L.L.: experimental design, paper preparation, and funding acquisition.

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Correspondence to Liwei Lu.

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Ma, K., Du, W., Xiao, F. et al. IL-17 sustains the plasma cell response via p38-mediated Bcl-xL RNA stability in lupus pathogenesis. Cell Mol Immunol (2020).

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  • Systemic lupus erythematosus (SLE)
  • Plasma cell (PC)
  • Autoantibody
  • Interleukin-17A (IL-17)