Immunoregulatory functions of KLRG1 cadherin interactions are dependent on forward and reverse signaling
Immunoregulatory functions of KLRG1 cadherin interactions are dependent on forward and reverse signaling
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DOI：
10.1182/blood-2009-06-228353
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发表时间：
2009-12-17
期刊：
影响因子：
20.3
通讯作者：
Brossay, Laurent
中科院分区：
文献类型：
--
作者：
Banh, Cindy;Fugere, Celine;Brossay, Laurent
KLRG1是一种抑制受体，在成熟T细胞和NK细胞亚群上表达。最近，E-、N-和r -钙粘蛋白被鉴定为KLRG1的配体。钙粘蛋白是一大家族的跨膜或膜相关糖蛋白，被认为只与其他钙粘蛋白特异性结合，以Ca2+依赖的方式介导细胞间的特异性粘附。钙粘蛋白KLRG1分子相互作用的后果尚未得到很好的表征。在这里，我们报告了钙粘蛋白的前2个细胞外结构域足以启动klrg1依赖性信号传导。我们还证明，KLRG1参与抑制钙粘蛋白依赖的细胞粘附，影响树突状细胞分泌炎症细胞因子，从而发挥免疫抑制作用。与此一致的是，KLRG1分子与钙粘蛋白结合可诱导钙粘蛋白酪氨酸磷酸化。因此，KLRG1/cadherin相互作用导致双向信号的产生，其中KLRG1和cadherin同时激活下游信号级联。综上所述，我们的研究结果为KLRG1和E-cadherin相互作用如何整合以差异调节KLRG1（+）细胞和E-cadherin表达细胞（如树突状细胞）提供了新的见解。[血液。2009;114:5299-5306]
KLRG1 is an inhibitory receptor expressed on a subset of mature T and NK cells. Recently, E-, N-, and R-cadherin have been identified as ligands for KLRG1. Cadherins are a large family of transmembrane or membrane-associated glycoproteins that were thought to only bind specifically to other cadherins to mediate specific cell-to-cell adhesion in a Ca2+-dependent manner. The consequences of cadherin KLRG1 molecular interactions are not well characterized. Here, we re-port that the first 2 extracellular domains of cadherin are sufficient to initiate a KLRG1-dependent signaling. We also demonstrate that KLRG1 engagement inhibits cadherin-dependent cellular adhesion and influences dendritic cell secretion of inflammatory cytokines, thereby exerting immunosuppressive effects. Consistent with this, engagement of cadherin by KLRG1 molecule induces cadherin tyrosine phosphorylation. Therefore, KLRG1/cadherin interaction leads to the generation of a bidirectional signal in which both KLRG1 and cadherin activate downstream signaling cascades simultaneously. Taken together, our results provide novel insights on how KLRG1 and E-cadherin interactions are integrated to differentially regulate not only KLRG1(+) cells, but also E-cadherin-expressing cells, such as dendritic cells. (Blood. 2009; 114: 5299-5306)