MRC Centre for Inflammation Research, Centre for MS Research, University of Edinburgh, UK.
Immunobiology. 2012 Feb;217(2):169-75. doi: 10.1016/j.imbio.2011.06.003. Epub 2011 Jul 13.
CD46 is a ubiquitously expressed type I transmembrane protein, first identified as a regulator of complement activation, and later as an entry receptor for a variety of pathogens. The last decade has also revealed the role of CD46 in regulating the adaptive immune response, acting as an additional costimulatory molecule for human T cells and inducing their differentiation into Tr1 cells, a subset of regulatory T cells. Interestingly, CD46 regulatory pathways are defective in T cells from patients with multiple sclerosis, asthma and rheumatoid arthritis, illustrating its importance in regulating T cell homeostasis. Indeed, CD46 expression at the cell surface is tightly regulated in many different cell types, highlighting its importance in several biological processes. Notably, CD46 is the target of enzymatic processing, being cleaved by metalloproteinases and by the presenilin/gamma secretase complex. This processing is required for its functions, at least in T cells. This review will summarize the latest updates on the regulation of CD46 expression and on its effects on T cell activation.
CD46 是一种广泛表达的 I 型跨膜蛋白，最初被鉴定为补体激活的调节剂，后来又被鉴定为多种病原体的进入受体。过去十年还揭示了 CD46 在调节适应性免疫反应中的作用，作为人类 T 细胞的另一个共刺激分子，并诱导其分化为 Tr1 细胞，即调节性 T 细胞的一个亚群。有趣的是，多发性硬化症、哮喘和类风湿关节炎患者的 T 细胞中存在 CD46 调节途径缺陷，这表明其在调节 T 细胞稳态中的重要性。事实上，许多不同类型的细胞中，CD46 表面表达受到严格调控，这突显了其在多个生物学过程中的重要性。值得注意的是，CD46 是酶切加工的靶标，可被金属蛋白酶和早老素/γ 分泌酶复合物切割。这种加工对于其功能是必需的，至少在 T 细胞中是这样。这篇综述将总结 CD46 表达调控及其对 T 细胞激活影响的最新进展。
