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/jci200317573
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发表时间：
2003-05-01
影响因子：
15.9
通讯作者：
Lakkis, FG
中科院分区：
文献类型：
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作者：
Goldstein, DR;Tesar, BM;Lakkis, FG
toll样受体（TLRs）是最近在apc上发现的种系编码受体，在微生物病原体的先天免疫识别中起着至关重要的作用。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，我们采用了靶向缺失通用TLR信号接头蛋白MyD88的小鼠皮肤同种异体移植模型。我们报道，在没有MyD88信号的情况下，不可能发生轻微的抗原错配（hy错配）同种异体移植排斥反应。此外，我们发现不能排斥这些同种异体移植物是由于引流淋巴结中成熟dc数量减少，导致抗移植物反应性T细胞的产生受损和Th1免疫受损。因此，这项工作表明tlr可以在移植环境中激活，而不仅仅是由感染激活。这些结果将先天免疫与适应性同种免疫反应的启动联系起来。
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.