Cutting edge: T cell Ig mucin-3 reduces inflammatory heart disease by increasing CTLA-4 during innate immunity
Cutting edge: T cell Ig mucin-3 reduces inflammatory heart disease by increasing CTLA-4 during innate immunity
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DOI：
10.4049/jimmunol.176.11.6411
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发表时间：
2006-06-01
影响因子：
4.4
通讯作者：
Fairweather, DeLisa
中科院分区：
文献类型：
--
作者：
Frisancho-Kiss, Sylvia;Nyland, Jennifer F.;Fairweather, DeLisa
如果适当下调促炎性免疫应答，可以减少甚至预防自身免疫性疾病。受体（如CTLA-4）、细胞因子（如TGF-β）和特化细胞（如CD 4（+）CD 25（+）T调节细胞）共同作用，以控制免疫反应。T细胞IG粘蛋白（Tim）家族蛋白是炎症的关键调节因子，提供抑制促炎反应的抑制信号，从而减少自身免疫和过敏反应。我们在这项研究中表明，在BALB/c小鼠对病毒感染的先天免疫应答过程中，减少Tim-3信号传导会减少肥大细胞和巨噬细胞上的CD 80共刺激分子表达，并降低CD 4（+）T细胞中的先天CTLA-4水平，导致调节性T细胞群减少和炎性心脏病增加。这些结果表明，心脏中炎症的调节在先天免疫期间开始，并且先天免疫系统细胞上的Tim-3信号传导严重影响适应性免疫应答的调节。
Autoimmune diseases can be reduced or even prevented if proinflammatory immune responses are appropriately down-regulated. Receptors (such as CTLA-4), cytokines (such as TGF-beta), and specialized cells (such as CD4(+) CD25(+) T regulatory cells) work together to keep immune responses in check. T cell Ig mucin (Tim) family proteins are key regulators of inflammation, providing an inhibitory signal that dampens proinflammatory responses and thereby reducing autoimmune and allergic responses. We show in this study that reducing Tim-3 signaling during the innate immune response to viral infection in BALB/c mice reduces CD80 costimulatory molecule expression on mast cells and macrophages and reduces innate CTLA-4 levels in CD4(+) T cells, resulting in decreased T regulatory cell populations and increased inflammatory heart disease. These results indicate that regulation of inflammation in the heart begins during innate immunity and that Tim-3 signaling on cells of the innate immune system critically influences regulation of the adaptive immune response.