Role of TLRs and DAMPs in allograft inflammation and transplant outcomes.
Role of TLRs and DAMPs in allograft inflammation and transplant outcomes.
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DOI：
10.1038/nrneph.2016.41
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发表时间：
2016-05
期刊：
影响因子：
--
通讯作者：
Goldstein DR
中科院分区：
文献类型：
--
作者：
Braza F;Brouard S;Chadban S;Goldstein DR
移植物炎症损害实体器官移植耐受的诱导并增强急性和慢性排斥反应。阐明器官移植后诱导炎症的机制可能会导致新的治疗方法来改善移植结果。在这篇综述中，我们描述了内源性物质-损伤相关分子模式（DAMP）-在同种异体移植物再灌注后释放并诱导炎症。我们还描述了实体器官移植后激活的先天免疫信号传导途径，重点是Toll样受体（TLR）及其信号适配器MYD 88。实验和临床研究已经产生了大量的证据，表明TLR和MYD 88有助于引发同种异体移植物炎症并促进急性和慢性排斥反应的发展。正在进行的临床研究正在测试实体器官移植中的TLR抑制策略，尽管避免损害宿主对病原体的防御是一个关键挑战。进一步阐明无菌炎症在同种异体移植物中诱导、维持和放大的机制，有可能导致新的抗炎治疗，从而改善实体器官移植受者的预后。
Graft inflammation impairs the induction of solid organ transplant tolerance and enhances acute and chronic rejection. Elucidating the mechanisms by which inflammation is induced after organ transplantation could lead to novel therapeutics to improve transplant outcomes. In this Review we describe endogenous substances — damage-associated molecular patterns (DAMPs) — that are released after allograft reperfusion and induce inflammation. We also describe innate immune signalling pathways that are activated after solid organ transplantation, with a focus on Toll-like receptors (TLRs) and their signal adaptor, MYD88. Experimental and clinical studies have yielded a large body of evidence that TLRs and MYD88 are instrumental in initiating allograft inflammation and promoting the development of acute and chronic rejection. Ongoing clinical studies are testing TLR inhibition strategies in solid organ transplantation, although avoiding compromising host defence to pathogens is a key challenge. Further elucidation of the mechanisms by which sterile inflammation is induced, maintained and amplified within the allograft has the potential to lead to novel anti-inflammatory treatments that could improve outcomes for solid organ transplant recipients.
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