MyD88-dependent induction of allergic Th2 responses to intranasal antigen
MyD88-dependent induction of allergic Th2 responses to intranasal antigen
复制标题
DOI：
10.1172/jci200522462
复制
发表时间：
2005-02-01
影响因子：
15.9
通讯作者：
Bottomly, K
中科院分区：
文献类型：
--
作者：
Piggott, DA;Eisenbarth, SC;Bottomly, K
MyD 88是一种常见的Toll样受体（TLR）衔接分子，被发现对诱导适应性Th 1免疫至关重要。相反，先天控制的适应性Th 2免疫已被证明是发生在一个MyD 88独立的方式。在这项研究中，我们表明，MyD 88是一个必不可少的先天性组成部分，在诱导TLR 4依赖性Th 2反应鼻内抗原，因此，我们证明了我们认为是一个新的作用MyD 88在肺Th 2免疫。诱导MyD 88-独立的I型IFN对LPS的应答在肺环境中是有缺陷的。此外，在缺乏MyD 88的情况下，LPS诱导的肺DC上共刺激分子表达的上调是有缺陷的，与骨髓来源的DC（BMDC）所观察到的相反。Th 2应答的重建发生在将活化的BMDC过继性肺转移至MyD 88缺陷受体后。此外，Th 2应答对MyD 88的依赖性受抗原暴露的初始途径的支配;这证明了我们所认为的用于控制适应性Th 2免疫的新的位点特异性先天机制。
MyD88 is a common Toll-like receptor (TLR) adaptor molecule found to be essential for induction of adaptive Th1 immunity. Conversely, innate control of adaptive Th2 immunity has been shown to occur in a MyD88-independent manner. In this study, we show that MyD88 is an essential innate component in the induction of TLR4-dependent Th2 responses to intranasal antigen; thus we demonstrate what we believe to be a novel role for MyD88 in pulmonary Th2 immunity. Induction of the MyD88-independent type I IFN response to LPS is defective in the pulmonary environment. Moreover, in the absence of MyD88, LPS-induced upregulation of costimulatory molecule expression on pulmonary DCs is defective, in contrast to what has been observed with bone marrow-derived DCs (BMDCs). Reconstitution of Th2 responses occurs upon adoptive pulmonary transfer of activated BMDCs to MyD88-deficient recipients. Furthermore, the dependence of Th2 responses on MyD88 is governed by the initial route of antigen exposure; this demonstrates what we believe are novel site-specific innate mechanisms for control of adaptive Th2 immunity.