IFN-beta promotes RSAD2 expression and Lupus plasma cell differentiation via DNA Demethylation

Abstract

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disease, in which the pathogenesis is revealed as abnormalities in B cells with no clear mechanism. Radical s-adenosyl methionine domain-containing 2 (RSAD2) is an interferon-stimulated gene (ISG), and it has been found to play an important role in innate immunity. Recent years the function of RSAD2 in autoimmune diseases, but its still unknown for RSAD2 in B cells from SLE patients still. Result In this study, we found RSAD2 was abnormal in SLE by analysis of database, which was relative with interferon (IFN). Further, we found that RSAD2 in peripheral blood B cell subsets was generally higher in SLE patients than healthy controls (HCs). In the meantime, differentiated B cells showed significantly higher expression of RSAD2 than naïve B cells in human tonsils. In the functional study in vitro, the frequencies of differentiated B cells and the expression of RSAD2 were enhanced by interferon-β (IFN-β). Simultaneously, the frequency of plasma cells (PC) was significantly reduced in sorted peripheral CD19+ B cells which was knock-down RSAD2 and stimulated with IFN-β. Mechanically, IFN-β can induce the hypomethylation of RSAD2 in B cells in vitro, which might be one of mechanisms for increased expression level of RSAD2 in B cells from SLE patients. Conclusion This study uncovered that IFN-β up-regulated the expression of RSAD2 by down-regulating the methylation of it to promote B cell differentiation.