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 Fc‐receptor like‐3 (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 interleukin 10 (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 lipopolysaccharide (LPS) promoted FCRL3 expression in a dose‐ and time‐dependent manner, thereby promoting IL‐10 secretion. LPS regulated Src homology region 2 domain‐containing phosphatase‐1 (SHP‐1) expression and p38 mitogen‐activated protein kinase (MAPK) pathway activation through FCRL3, and FCRL3 upregulated the SHP‐1 expression and p38 phosphorylation levels. When SHP‐1 small interfering RNA 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 (tumor necrosis factor‐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.

中文翻译：

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FCRL3通过SHP-1和p38 MAPK信号通路促进B细胞中IL-10的表达。

多发性硬化症（MS）是中枢神经系统的一种自身免疫性疾病，是由遗传和环境因素的相互作用引起的。当前的研究表明Fc受体样3（FCRL3）与MS密切相关，但尚未阐明FCRL3在MS中的具体作用。这项研究进一步发现，MS患者中FCRL3和白介素10（IL-10）的表达下调，但缓解期这些蛋白的表达高于急性期。rs7528684的C等位基因与MS相关，而CC基因型可能导致FCRL3表达上调和IL-10分泌增加。进一步的B细胞体外实验发现，脂多糖（LPS）以剂量和时间依赖性方式促进FCRL3表达，从而促进IL-10分泌。LPS通过FCRL3调节Src同源区域2结构域的磷酸酶-1（SHP-1）表达和p38丝裂原活化蛋白激酶（MAPK）途径的激活，而FCRL3上调SHP-1表达和p38磷酸化水平。当添加SHP-1小干扰RNA或p38途径抑制剂时，FCRL3对IL-10分泌的作用被显着抑制。此外，FCRL3抑制炎症因子（肿瘤坏死因子-α，IL-1β，IL-6和IL-8）的分泌。抑制IL-10的表达后，FCRL3的上述作用被阻断。这些结果表明，FCRL3可以激活SHP-1和p38 MAPK途径，然后促进B细胞中IL-10的分泌，从而抑制炎症因子的分泌。因此，FCRL3可能在MS中起免疫保护作用，