Pattern recognition scavenger receptor SRA/CD204 down-regulates Toll-like receptor 4 signaling-dependent CD8 T-cell activation
Pattern recognition scavenger receptor SRA/CD204 down-regulates Toll-like receptor 4 signaling-dependent CD8 T-cell activation
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DOI：
10.1182/blood-2008-11-190033
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发表时间：
2009-06-04
期刊：
影响因子：
20.3
通讯作者：
Wang, Xiang-Yang
中科院分区：
文献类型：
--
作者：
Yi, Huanfa;Yu, Xiaofei;Wang, Xiang-Yang
A类清道夫受体（SRA），也称为CD 204，已被证明参与动脉粥样硬化的发病机制和病原体感染的模式识别。然而，它在适应性免疫反应中的作用尚未得到很好的定义。在这项研究中，我们报告了SRA/CD 204的缺乏促进了Toll样受体（TLR）4激动剂增强的肿瘤保护性免疫，这与增强的CD 8（+）效应T细胞活化和改善的肿瘤生长抑制有关。SRA/CD 204缺陷的树突状细胞（DCs）在TLR 4结合后显示出比野生型对应物更有效的免疫刺激活性。通过RNA干扰沉默SRA/CD 204提高了DC引发抗原特异性CD 8（+）T细胞的能力，表明抗原呈递细胞，例如DC，在SRA/CD 204介导的免疫调节中起主要作用。我们的研究结果揭示了SRA/CD 204（一种非TLR模式识别受体）作为TLR 4介导的免疫后果的生理负调节剂的先前未被认识的作用，这对TLR靶向免疫干预的发展具有重要的临床意义。（血。2009; 113：5819-5828）
Class A scavenger receptor (SRA), also known as CD204, has been shown to participate in the pathogenesis of atherosclerosis and the pattern recognition of pathogen infection. However, its role in adaptive immune responses has not been well defined. In this study, we report that the lack of SRA/CD204 promotes Toll-like receptor (TLR)4 agonist-augmented tumor-protective immunity, which is associated with enhanced activation of CD8(+) effector T cell and improved inhibition of tumor growth. Dendritic cells (DCs) deficient in SRA/CD204 display more effective immunostimulatory activities upon TLR4 engagement than those from wild-type counterparts. Silencing of SRA/CD204 by RNA interference improves the ability of DCs to prime antigen-specific CD8(+) T cells, suggesting that antigen-presenting cells, for example, DCs, play a major role in SRA/CD204-mediated immune modulation. Our findings reveal a previously unrecognized role for SRA/CD204, a non-TLR pattern recognition receptor, as a physiologic negative regulator of TLR4-mediated immune consequences, which has important clinical implications for development of TLR-targeted immunotherapeutic intervention. (Blood. 2009; 113: 5819-5828)