Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
Ann N Y Acad Sci. 2010 Oct;1209:91-8. doi: 10.1111/j.1749-6632.2010.05745.x.
Calreticulin (CRT) plays a role in the clearance of dying cells and has been implicated in autoimmunity. Recent evidence indicates that cell surface CRT (csCRT) acts as a signal transducing receptor for the rheumatoid arthritis (RA) shared epitope (SE). The SE binding site on CRT has been mapped to amino acid residues 217-223 in the P-domain. Upon interaction with dendritic cells (DCs), the SE activates potent immune regulatory events. In CD8α(+) DCs, which express higher abundance of csCRT, the SE inhibits the tolerogenic enzyme indoleamine 2,3 dioxygenase with resultant inhibition of regulatory T (Treg) cell differentiation. In CD8α(-) DCs, the SE ligand increases secretion of IL-6 and IL-23 and facilitates generation of Th17 cells, a T cell subset known to play a role in autoimmunity. On the basis of these recent findings, we discuss the possibility that the csCRT may play a pathogenic role in RA by transducing SE-activated Th17-polarizing signals.
钙网蛋白（CRT）在清除死亡细胞中发挥作用，并与自身免疫有关。最近的证据表明，细胞表面 CRT（csCRT）作为类风湿关节炎（RA）共享表位（SE）的信号转导受体。CRT 上的 SE 结合位点已被映射到 P 结构域中的氨基酸残基 217-223。与树突状细胞（DCs）相互作用时，SE 会激活有效的免疫调节事件。在表达更高丰度 csCRT 的 CD8α(+) DCs 中，SE 抑制了具有免疫抑制作用的酶吲哚胺 2,3 双加氧酶，从而抑制了调节性 T（Treg）细胞的分化。在 CD8α(-) DCs 中，SE 配体增加了 IL-6 和 IL-23 的分泌，并促进了 Th17 细胞的生成，Th17 细胞是一种已知在自身免疫中发挥作用的 T 细胞亚群。基于这些最近的发现，我们讨论了 csCRT 通过转导 SE 激活的 Th17 极化信号，在 RA 中发挥致病作用的可能性。
