Immunology Unit, Department of Cell Biology, Immunology and Neurosciences, Medical School, University of Barcelona , Barcelona , Spain.
Front Immunol. 2013 Jul 31;4:225. doi: 10.3389/fimmu.2013.00225. eCollection 2013.
The Signaling Lymphocyte Activation Molecule Family (SLAMF) genes, which encode cell-surface receptors that modulate innate and adaptive immune responses, lay within a genomic region of human and mouse chromosome 1 that confers a predisposition for the development of systemic lupus erythematosus (SLE). Herein, we demonstrate that the SLAMF member Ly9 arises as a novel receptor contributing to the reinforcement of tolerance. Specifically, Ly9-deficient mice spontaneously developed features of systemic autoimmunity such as the production of anti-nuclear antibodies (ANA), -dsDNA, and -nucleosome autoantibodies, independently of genetic background [(B6.129) or (BALB/c.129)]. In aged (10- to 12-month-old) Ly9 (-/-) mice key cell subsets implicated in autoimmunity were expanded, e.g., T follicular helper (Tfh) as well as germinal center (GC) B cells. More importantly, in vitro functional experiments showed that Ly9 acts as an inhibitory receptor of IFN-γ producing CD4(+) T cells. Taken together, our findings reveal that the Ly9 receptor triggers cell intrinsic safeguarding mechanisms to prevent a breach of tolerance, emerging as a new non-redundant inhibitory cell-surface receptor capable of disabling autoantibody responses.
信号淋巴细胞激活分子家族（SLAMF）基因，编码调节先天和适应性免疫反应的细胞表面受体，位于人类和小鼠 1 号染色体的基因组区域内，该区域易导致系统性红斑狼疮（SLE）的发生。在此，我们证明 SLAMF 成员 Ly9 是一种新的受体，有助于增强耐受性。具体而言，Ly9 缺陷小鼠自发地表现出系统性自身免疫的特征，如产生抗核抗体（ANA）、双链 DNA（dsDNA）和核小体自身抗体，而与遗传背景无关[(B6.129)或（BALB/c.129)]。在老年（10-12 个月大）Ly9（-/-）小鼠中，与自身免疫有关的关键细胞亚群被扩增，例如滤泡辅助性 T 细胞（Tfh）和生发中心（GC）B 细胞。更重要的是，体外功能实验表明，Ly9 作为 IFN-γ 产生的 CD4（+）T 细胞的抑制性受体发挥作用。综上所述，我们的研究结果表明，Ly9 受体触发细胞内在的保护机制，以防止耐受性的破坏，作为一种新的非冗余抑制性细胞表面受体，能够使自身抗体反应失效。
