Absence of innate MyD88 signaling promotes inducible allograft acceptance
Absence of innate MyD88 signaling promotes inducible allograft acceptance
复制标题
DOI：
10.4049/jimmunol.177.8.5307
复制
发表时间：
2006-10-15
影响因子：
4.4
通讯作者：
Goldstein, Daniel R.
中科院分区：
文献类型：
--
作者：
Walker, Wendy E.;Nasr, Isam W.;Goldstein, Daniel R.
以前诱导移植耐受的实验策略主要集中在修改适应性免疫上。然而，关于先天免疫信号在诱导移植耐受中的作用，我们知之甚少。使用一个高免疫原性的小鼠皮肤移植模型，当天然免疫被保留时，该模型抵抗移植耐受诱导，我们发现，缺乏关键的先天Toll样受体信号适配器MyD88，消除了这种抵抗，并促进了可诱导的同种异体移植接受。在我们的模型中，MyD88的缺失会损害炎性树突状细胞的反应，从而减少T细胞的激活。这一效应增加了T细胞对由CD4(+)CD25(+)调节性T细胞介导的抑制的敏感性。因此，这项研究提供了证据，表明MyD88的缺失促进了同种异体移植的可诱导性接受，并暗示抑制天然免疫可能是促进移植耐受的一种潜在的、临床相关的策略。
Prior experimental strategies to induce transplantation tolerance have focused largely on modifying adaptive immunity. However, less is known concerning the role of innate immune signaling in the induction of transplantation tolerance. Using a highly immunogenic murine skin transplant model that resists transplantation tolerance induction when innate immunity is preserved, we show that absence of MyD88, a key innate Toll like receptor signal adaptor, abrogates this resistance and facilitates inducible allograft acceptance. In our model, absence of MyD88 impairs inflammatory dendritic cell responses that reduce T cell activation. This effect increases T cell susceptibility to suppression mediated by CD4(+)CD25(+) regulatory T cells. Therefore, this study provides evidence that absence of MyD88 promotes inducible allograft acceptance and implies that inhibiting innate immunity may be a potential, clinically relevant strategy to facilitate transplantation tolerance.