TIM genes: a family of cell surface phosphatidylserine receptors that regulate innate and adaptive immunity.
TIM genes: a family of cell surface phosphatidylserine receptors that regulate innate and adaptive immunity.
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DOI：
10.1111/j.0105-2896.2010.00903.x
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发表时间：
2010-05
影响因子：
8.7
通讯作者：
DeKruyff RH
中科院分区：
文献类型：
--
作者：
Freeman GJ;Casasnovas JM;Umetsu DT;DeKruyff RH
TIM（T细胞/跨膜、免疫球蛋白和粘蛋白）基因家族在调节免疫应答（包括过敏、哮喘、移植耐受、自身免疫和对病毒感染的应答）中起关键作用。TIM免疫球蛋白可变区结构域的独特结构允许高度特异性地识别暴露在凋亡细胞表面上的磷脂酰丝氨酸（PtdSer）。TIM-1、TIM-3和TIM-4均识别PtdSer，但表达不同，表明它们在调节免疫应答中具有不同的功能。TIM-1是哮喘和变态反应的重要易感基因，优先表达于辅助性T细胞2（Th 2）上，并作为T细胞活化的有效共刺激分子发挥功能。TIM-3优先在Th 1和Tc 1细胞上表达，并产生导致Th 1和Tc 1细胞凋亡的抑制信号。TIM-3也在一些树突状细胞上表达，并且可以介导凋亡细胞的吞噬作用和抗原的交叉呈递。相反，TIM-4仅在抗原呈递细胞上表达，在那里它介导凋亡细胞的吞噬作用，并在维持耐受性中起重要作用。因此，TIM分子提供了用于识别凋亡细胞的功能库，其决定凋亡细胞识别是否导致免疫激活或耐受，这取决于所接合的TIM分子及其表达的细胞类型。
The TIM (T cell/transmembrane, immunoglobulin, and mucin) gene family plays a critical role in regulating immune responses, including allergy, asthma, transplant tolerance, autoimmunity, and the response to viral infections. The unique structure of TIM immunoglobulin variable region domains allows highly specific recognition of phosphatidylserine (PtdSer), exposed on the surface of apoptotic cells. TIM-1, TIM-3, and TIM-4 all recognize PtdSer but differ in expression, suggesting that they have distinct functions in regulating immune responses. TIM-1, an important susceptibility gene for asthma and allergy, is preferentially expressed on T-helper 2 (Th2) cells and functions as a potent costimulatory molecule for T-cell activation. TIM-3 is preferentially expressed on Th1 and Tc1 cells, and generates an inhibitory signal resulting in apoptosis of Th1 and Tc1 cells. TIM-3 is also expressed on some dendritic cells and can mediate phagocytosis of apoptotic cells and cross-presentation of antigen. In contrast, TIM-4 is exclusively expressed on antigen-presenting cells, where it mediates phagocytosis of apoptotic cells and plays an important role in maintaining tolerance. TIM molecules thus provide a functional repertoire for recognition of apoptotic cells, which determines whether apoptotic cell recognition leads to immune activation or tolerance, depending on the TIM molecule engaged and the cell type on which it is expressed.
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