LAUSR

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that is caused by the interaction of genetic and environmental factors. Current studies have shown that FCRL3 is closely related to MS, but the specific role of FCRL3 in MS has not yet been clarified. This study further found that FCRL3 and IL-10 expression was downregulated in MS patients, but the expression of these proteins was higher in the remission phase than that in the acute phase. The C allele of rs7528684 was associated with MS, and the CC genotype could lead to the upregulation of FCRL3 expression and the increase in IL-10 secretion. Further in vitro experiments with B cells found that LPS promoted FCRL3 expression in a dose- and time-dependent manner, thereby promoting IL-10 secretion. LPS regulated SHP-1 expression and p38 MAPK pathway activation through FCRL3, and FCRL3 upregulated the SHP-1 expression and p38 phosphorylation levels. When SHP-1 siRNA or a p38 pathway inhibitor was added, the effect of FCRL3 on IL-10 secretion was significantly inhibited. In addition, FCRL3 inhibited the secretion of inflammatory factors (TNF-α, IL-1β, IL-6 and IL-8); after inhibiting the expression of IL-10, the abovementioned effects of FCRL3 were blocked. These results suggest that FCRL3 can activate the SHP-1 and p38 MAPK pathways and then promote the secretion of IL-10 in B cells, thus inhibiting the secretion of inflammatory factors. Therefore, FCRL3 may play an immunoprotective role in MS, and it will be an effective target for the diagnosis and treatment of MS. This article is protected by copyright. All rights reserved.