Poly(I:C)pretreatment Suppresses B Cell-mediated Lupus-like Autoimmunity Through Induction Of Peli1

Systemic lupus erythematosus(SLE)is a multifactorial systemic autoimmune disease characterized by the deposition of immune complexes formed by the binding of a large number of pathogenic autoantibodies to autoantigens in patients,resulting in tissue damage and multiple organ lesions.Noncanonical NF-?B pathway is essential for the B cell activation and antibody production,which centralize the critical role of B cells in regulating the pathogenesis of SLE.We have previously demonstrated that Peli1 negatively regulate activation of noncanonical NF-?B signaling pathways and lupus autoimmunity.Here we show that Poly(I:C)is a potent inducer of Peli1 protein in mouse splenic B cells on a dose-and time-dependent manner,and Poly(I:C)-induced Peli1 protein dramatically suppressed the activation of noncanonical NF-?B pathway.In addition,Poly(I:C)pretreated B cells fail to induce lupus-like disease in BM12 CD4~+T cell-immunized mice.Accordingly,the induction of antibody-producing plasma cells and germinal center B cells,as well as the production of autoantibodies are significantly impaired in immunized?MT mice that transferred with Poly(I:C)pretreated B cells.Our findings demonstrated that Poly(I:C)-induced Peli1 negatively regulates the noncanonical NF-?B pathway in the context of restraining the pathogenesis of lupus-like disease.