Human leukocyte antigen (HLA)-G, a non-classical HLA class I molecule, has one of the splicing isoforms, HLA-G2, which lacks one domain (α2) and forms a non-covalent homodimer. HLA-G2 is expressed on placental cells, regulatory T cells, tumor cells, and virus-infected cells, and is involved in immunosuppression. The major isoform of HLA-G, HLA-G1, binds to leukocyte immunoglobulin (Ig)-like receptor (LILR) B1 and LILRB2, on the contrary, HLA-G2 binds to only LILRB2. We previously reported that HLA-G2 bound LILRB2 more strongly than HLA-G1 and also to paired Ig-like receptor (PIR)-B, a mouse homolog of LILRBs. Furthermore, HLA-G2 showed immunosuppressive effects in both collagen-induced arthritis (CIA) and atopic dermatitis-like model mice. In this study, we examine in vivo effects of HLA-G2 in systemic lupus erythematosus (SLE) model mice. HLA-G2 showed the suppression of the typical SLE symptoms such as serum anti-dsDNA antibody level and urinary albumin index. Furthermore, HLA-G2 tended to downregulate B-lymphocyte stimulator (BLyS) production. This is the first observation of the immunosuppressive effects of HLA-G2 isoform in SLE model mice, suggesting that HLA-G2 could be a useful therapeutic agent for SLE.

中文翻译：

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易患狼疮MRL / lpr小鼠的可溶性人白细胞抗原G2亚型的治疗作用。

人白细胞抗原（HLA）-G是一种非经典的HLA I类分子，具有一种剪接同工型HLA-G2，它缺少一个结构域（α2）并形成非共价同型二聚体。HLA-G2在胎盘细胞，调节性T细胞，肿瘤细胞和病毒感染的细胞上表达，并参与免疫抑制。HLA-G的主要同种型HLA-G1与白细胞免疫球蛋白（Ig）样受体（LILR）B1和LILRB2结合，相反，HLA-G2仅与LILRB2结合。我们先前曾报道，HLA-G2比HLA-G1更牢固地结合LILRB2，并且还与成对的Ig样受体（PIR）-B（LILRB的小鼠同源物）结合。此外，HLA-G2在胶原诱导的关节炎（CIA）和特应性皮炎样模型小鼠中均显示出免疫抑制作用。在这项研究中，我们检查了HLA-G2在系统性红斑狼疮（SLE）模型小鼠中的体内作用。HLA-G2显示出对典型SLE症状的抑制，例如血清抗dsDNA抗体水平和尿白蛋白指数。此外，HLA-G2倾向于下调B淋巴细胞刺激物（BLyS）的产生。这是对SLE模型小鼠中HLA-G2同种型免疫抑制作用的首次观察，表明HLA-G2可能是SLE的有用治疗剂。