Peli1 Regulated Systemic Lupus Erythematosus

Systemic lupus erythematosus(SLE)is a systemic autoimmune disease with various clinical manifestations.The pathogenesis of SLE is strongly associated with loss of B cell tolerance and sustained autoantibody production.And that the interaction between Tfh cells and B cells in the germinal center(GC)is important for GC activation.Non-canonical NF-?B signaling mediates B cells activation and antibody production.In previous studies,we found that the E3 ubiquitin ligase Peli1 inhibits non-canonical NF-?B signaling pathways activation and lupus-like autoimmune disease.Here we demonstrated that Poly(I:C)is a potent inducer of Peli1,and Poly(I:C)-induced Peli1 significantly suppressed translocation of transcriptional factors RelB and p52 into the nuclear,thereby suppressing non-classical NF-?B signaling pathways.Moreover,B cells pretreated with Poly(I:C)were transferred to?MT mice together with CD4~+T cells from BM12 mice,which failed to induce lupus-like disease,and the production of autoantibodies was dramatically inhibited.We also found that the proportion of Tfh cells in peripheral blood mononuclear cells of SLE patients was higher than that of normal people.Interestingly,the loss of Peli1 could promote Tfh cell differentiation.It follows that Peli1 not only suppressed B cell activation and autoantibody production by negatively regulating non-classical NF-?B signaling,but also regulated Tfh cell differentiation.Peli1 regulated the pathogenesis of lupus-like disease in various aspects and cells.