Identification of the ligands for KLRG1, an inhibitory receptor expressed on NK cells.

后生动物的身体受到免疫系统的保护。脊椎动物的免疫系统由获得性免疫和先天免疫组成。自然杀伤(NK)细胞在天然免疫中发挥着关键作用，尤其是对癌细胞和细胞内病原体的免疫。NK细胞对靶细胞的识别涉及具有相反功能的NK细胞受体：抑制性受体和激活性受体。这些受体的信号平衡决定了NK细胞的激活。已知的抑制性NK细胞受体的配体大多为MHC-I类分子，它们被认为是自身的标志。然而，NK细胞对靶细胞的识别并不完全依赖于MHC I类分子。实际上，NK细胞表达配体未知的抑制性受体，其中包括KLRG1。KLRG1是一种凝集素样抑制性受体，表达于NK和T细胞亚群。KLRG1的表达也受感染的调节。在目前的研究中，我们的团队确定了三个经典的钙粘附素，它们通过同型相互作用促进细胞-细胞黏附，作为KLRG1的配体。我们还发现E-钙粘素连接KLRG1抑制了NK细胞的毒性。由于KLRG1识别的经典钙粘附素在体内广泛分布，KLRG1可能参与了感染诱导的免疫反应的终止。E-钙粘附素在恶性肿瘤中的表达经常丢失或减弱，这一观点提出了KLRG1表达的NK细胞可能在恶性肿瘤监测中发挥作用的可能性。目前的研究提供了一个新的概念，即钙粘附素通过识别KLRG1而参与免疫反应的调节。

Bodies of the metazoan organisms are protected by the immune system. The immune system of vertebrates consists of acquired and innate immunity. Natural killer (NK) cells play pivotal roles in innate immunity especially against cancer cells and intracellular pathogens. NK cell recognition of targets involves NK cell receptors with opposing functions: inhibitory receptors and activating receptors. Balance of signals from these receptors decides activation of NK cells. Most of the known ligands for the inhibitory NK cell receptors are MHC class I molecules, which are considered as markers of self. However, NK cell recognition of targets is not solely depend on MHC class I. Indeed, NK cells express inhibitory receptors of which ligands are unidentified, which include KLRG1. KLRG1 is a lectin-like inhibitory receptor expressed on subsets of NK and T cells. Expression of KLRG1 is also regulated by infection. In the present study, our group identified three classical cadherins, which contribute to cell-cell adhesion through homotypic interaction, as ligands for KLRG1. We also showed that ligation of KLRG1 by E-cadherin inhibit NK cell ctyotoxocity. Because the classical cadherins that KLRG1 recognizes are distributed ubiquitously among the body, KLRG1 may contribute to the termination of immune response induced by infection. The notion that expression of E-cadherin is often lost or attenuated in malignant carcinoma raises a possibility that KLRG1-expressing NK cells may play a role in malignant tumor surveillance. The current study provides a new concept that cadherins contribute to regulation of immune response through recognition by KLRG1.