Critical role of the Toll-like receptor signal adaptor protein MyD88 in acute allograft rejection.
Critical role of the Toll-like receptor signal adaptor protein MyD88 in acute allograft rejection.
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DOI：
10.1172/jci17573
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发表时间：
2003-05
期刊：
影响因子：
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通讯作者：
D. Goldstein;B. Tesar;S. Akira;Fadi G Lakkis
中科院分区：
文献类型：
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作者：
D. Goldstein;B. Tesar;S. Akira;Fadi G Lakkis
Toll样受体（Toll like receptors，TLR）是近年来发现的一种存在于APC上的生殖细胞编码的受体，在病原微生物的先天免疫识别中起着重要作用。然而，它们在实体器官移植中的作用尚不清楚。为了探索这一作用，我们采用了一种皮肤同种异体移植模型，使用靶向缺失通用TLR信号衔接蛋白MyD 88的小鼠。我们报告说，轻微的抗原不匹配（HY-不匹配）同种异体排斥反应不会发生在MyD 88信号的情况下。此外，我们表明，无法拒绝这些同种异体移植物的结果从引流淋巴结中的成熟DC的数量减少，导致抗移植物反应性T细胞的产生受损和受损的Th 1免疫。因此，这项工作表明TLR可以在移植环境中被激活，而不仅仅是感染。这些结果将先天免疫与适应性同种免疫应答的启动联系起来。
The Toll-like receptors (TLRs) are recently discovered germline-encoded receptors on APCs that are critically important in innate immune recognition of microbial pathogens. However, their role in solid-organ transplantation is unknown. To explore this role, we employed a skin allograft model using mice with targeted deletion of the universal TLR signal adaptor protein, MyD88. We report that minor antigen-mismatched (HY-mismatched) allograft rejection cannot occur in the absence of MyD88 signaling. Furthermore, we show that the inability to reject these allografts results from a reduced number of mature DCs in draining lymph nodes, leading to impaired generation of anti-graft-reactive T cells and impaired Th1 immunity. Hence, this work demonstrates that TLRs can be activated in a transplant setting and not solely by infections. These results link innate immunity to the initiation of the adaptive alloimmune response.