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

KLRG1 配体的鉴定，KLRG1 是 NK 细胞上表达的抑制性受体。

基本信息

批准号：
15590057
负责人：
MATSUMOTO Naoki
金额：
$ 2.37万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590057/
关键词：
NK cells T cells Innate immunity Lectin-like receptors KLRG1 ligand cadherins expression cloning 可溶型レセプターレセプター性状解析

项目摘要

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.

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后天免疫和先天免疫组成。自然杀伤（NK）细胞在先天免疫中起着关键作用，特别是针对癌细胞和细胞内病原体。NK细胞对靶标的识别涉及具有相反功能的NK细胞受体：抑制性受体和活化性受体。来自这些受体的信号的平衡决定NK细胞的激活。大多数已知的抑制性NK细胞受体的配体是MHC I类分子，其被认为是自身的标志物。然而，NK细胞对靶点的识别并不完全依赖于MHC I类。事实上，NK细胞表达抑制性受体，其配体未被鉴定，包括KLRG 1。KLRG 1是一种凝集素样抑制性受体，在NK和T细胞亚群上表达。KLRG 1的表达也受到感染的调节。在本研究中，我们的小组确定了三个经典的钙粘蛋白，这有助于细胞间粘附通过同型相互作用，作为配体KLRG 1。我们还发现，通过E-钙粘蛋白连接KLRG 1可以抑制NK细胞的细胞毒性。由于KLRG 1识别的经典钙粘蛋白广泛分布于机体，因此KLRG 1可能有助于终止感染诱导的免疫应答。在恶性肿瘤中E-钙粘蛋白的表达经常丢失或减弱的概念提出了表达KLRG 1的NK细胞可能在恶性肿瘤监视中发挥作用的可能性。目前的研究提供了一个新的概念，即钙粘蛋白通过识别KLRG 1来调节免疫反应。