Department of Immunology and the Walter M. and Helen D. Bader Center for Research on Arthritis and Autoimmune Disease, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Curr Opin Immunol. 2010 Dec;22(6):706-14. doi: 10.1016/j.coi.2010.10.014. Epub 2010 Nov 18.
The SLAM/CD2 gene family encodes receptors that play important roles in regulating multiple cellular interactions in the adaptive and innate immune systems. Three members of this gene family, Ly108, Ly9, and CD84, exhibit polymorphisms that strongly influence susceptibility to systemic autoimmunity, notably in mice, but also in some human populations. Polymorphisms of Ly108 in mice strongly impact central tolerance in both B and T cell development, predominantly by modulating apoptosis, anergy, and cell-cycle progression. In addition, Ly108 and CD84, together with their downstream signaling adaptor SLAM-associated protein (SAP), have emerged as key players in B-T interactions during the formation of germinal centers. Interestingly, several independent lines of research have now associated variations in B-T interactions during germinal center formation with systemic autoimmunity, suggesting that susceptibility to systemic lupus erythematosus (SLE) may involve in part the impairment of this peripheral tolerance checkpoint. These new insights into the multiplicity of roles played by the SLAM/CD2 family and its potential importance in human autoimmunity positions the SLAM/CD2 family as an excellent target for immunotherapy.
SLAM/CD2 基因家族编码的受体在调节适应性和先天免疫系统中的多种细胞相互作用中发挥重要作用。该基因家族的三个成员 Ly108、Ly9 和 CD84 表现出多态性，强烈影响系统性自身免疫易感性，这在小鼠中尤为明显，但在一些人类群体中也存在。小鼠 Ly108 的多态性强烈影响 B 和 T 细胞发育中的中枢耐受，主要通过调节细胞凋亡、无能和细胞周期进程。此外，Ly108 和 CD84 与其下游信号转导衔接蛋白 SLAM 相关蛋白 (SAP) 一起，成为生发中心形成过程中 B-T 相互作用的关键参与者。有趣的是，现在有几条独立的研究线索将生发中心形成过程中的 B-T 相互作用的变化与系统性红斑狼疮 (SLE) 易感性联系起来，这表明 SLE 的易感性可能部分涉及到外周耐受检查点的损害。SLAM/CD2 家族所扮演的多种角色的这些新见解及其在人类自身免疫中的潜在重要性，使 SLAM/CD2 家族成为免疫治疗的一个极好靶点。
