B cells control lupus autoimmunity by inhibiting Th17 and promoting Th22 cells
- Cell Death Dis. 2020 Mar 3;11(3):164. doi: 10.1038/s41419-020-2362-y.
- 1. Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China. [email protected].
- 2. Division of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China.
- 3. Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China.
- 4. Department of Immunology, Basic Medical School, Fudan University, Shanghai, China.
- 5. Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China.
- # Contributed equally.
B cells exert immunosuppressive effects and offer therapeutic potential for systemic lupus erythematosus (SLE), but the mechanism remains unclear. Here we analyzed the B cell regulation of Th17/Th22 cell differentiation in lupus and found that α-IgM- and α-CD40-activated B cells could inhibit Th17 and promote Th22 cell differentiation from naive T cells under Th17 Cell Culture conditions. B cell-induced Th22 cells demonstrated immunosuppressive effects and could decrease renal endothelial cell Apoptosis in vitro. Moreover, activated B cell infusion relieved lupus injuries via IL-22 production in vivo. Mechanically, activated B cells affected Th17/Th22 cell differentiation by non-contact TNF-α secretion and mTOR activation. Finally, activated B cells could affect Th17/Th22 cell differentiation in human peripheral blood T cells. These data suggest that activated B cells might attenuate lupus autoimmunity by inhibiting Th17 but promoting Th22 cell differentiation, supporting B cell activation as a promising therapeutic for the treatment of lupus.