Untangling Local Pro-Inflammatory, Reparative, and Regulatory Damage-Associated Molecular-Patterns (DAMPs) Pathways to Improve Transplant Outcomes.
Untangling Local Pro-Inflammatory, Reparative, and Regulatory Damage-Associated Molecular-Patterns (DAMPs) Pathways to Improve Transplant Outcomes.
复制标题
解开局部促炎、修复和调节损伤相关分子模式（DAMP）通路以改善移植结果。
DOI：
10.3389/fimmu.2021.611910
复制
发表时间：
2021
影响因子：
7.3
通讯作者：
Turnquist HR
中科院分区：
文献类型：
--
作者：
Dwyer GK;Turnquist HR
实体器官移植后的有害炎症反应是在免疫细胞感知到病原体相关分子模式（PAMP）和某些损伤相关分子模式（DAMP）时启动的，所述病原体相关分子模式和某些损伤相关分子模式在移植相关过程中释放或暴露，例如缺血/再灌注损伤（IRI）、手术创伤和受体调节。在实验研究中，这些炎症反应引发并传播抗同种异体抗原（AlloAg）反应，并靶向DAMP和PAMP，或它们激活的信号级联，减少同种异体免疫，并有助于改善同种异体实体器官移植后的结果。然而，DAMP也涉及启动特定免疫细胞，特别是Treg和巨噬细胞的基本抗炎和修复功能。有趣的是，DAMP信号传导也参与局部和全身稳态。在本文中，我们描述了新兴文献，这些文献定义了移植后的不良结局可能如何导致，不仅仅是由于过多的DAMP驱动的炎症，而是由于成功修复组织或重建组织稳态所需的DAMP或相关分子的子集存在不足。当这些稳态或修复信号被移植小生境中的同种异体反应性免疫细胞失调或劫持时，也可能出现不良结果。全面了解控制组织修复和体内平衡的关键途径，以及同种免疫反应或移植相关过程如何破坏这些途径，将导致新的免疫治疗药物，可以预防或逆转组织病理学，导致因慢性排斥而导致移植物丢失。
Detrimental inflammatory responses after solid organ transplantation are initiated when immune cells sense pathogen-associated molecular patterns (PAMPs) and certain damage-associated molecular patterns (DAMPs) released or exposed during transplant-associated processes, such as ischemia/reperfusion injury (IRI), surgical trauma, and recipient conditioning. These inflammatory responses initiate and propagate anti-alloantigen (AlloAg) responses and targeting DAMPs and PAMPs, or the signaling cascades they activate, reduce alloimmunity, and contribute to improved outcomes after allogeneic solid organ transplantation in experimental studies. However, DAMPs have also been implicated in initiating essential anti-inflammatory and reparative functions of specific immune cells, particularly Treg and macrophages. Interestingly, DAMP signaling is also involved in local and systemic homeostasis. Herein, we describe the emerging literature defining how poor outcomes after transplantation may result, not from just an over-abundance of DAMP-driven inflammation, but instead an inadequate presence of a subset of DAMPs or related molecules needed to repair tissue successfully or re-establish tissue homeostasis. Adverse outcomes may also arise when these homeostatic or reparative signals become dysregulated or hijacked by alloreactive immune cells in transplant niches. A complete understanding of the critical pathways controlling tissue repair and homeostasis, and how alloimmune responses or transplant-related processes disrupt these will lead to new immunotherapeutics that can prevent or reverse the tissue pathology leading to lost grafts due to chronic rejection.
登录
查看更多内容
影响因子：
3.7
作者：
Borges TJ;Porto BN;Teixeira CA;Rodrigues M;Machado FD;Ornaghi AP;de Souza AP;Maito F;Pavanelli WR;Silva JS;Bonorino C
通讯作者：
Bonorino C
DOI：
10.1038/nrneph.2016.41
发表时间：
2016-05
期刊：
Nature reviews. Nephrology
影响因子：
--
作者：
Braza F;Brouard S;Chadban S;Goldstein DR
通讯作者：
Goldstein DR
专门的促解决介质：感染和炎症的内源性调节剂。
DOI：
10.1038/nri.2015.4
发表时间：
2016-01
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Basil MC;Levy BD
通讯作者：
Levy BD
影响因子：
32.4
作者：
Buckley, Christopher D.;Gilroy, Derek W.;Serhan, Charles N.
通讯作者：
Serhan, Charles N.
影响因子：
4.4
作者：
Bronte, V;Serafini, P;Zanovello, P
通讯作者：
Zanovello, P