In Vivo Attenuation of Antibody-Mediated Acute Renal Allograft Rejection by Ex Vivo TGF-β-Induced CD4(+)Foxp3(+) Regulatory T Cells.
In Vivo Attenuation of Antibody-Mediated Acute Renal Allograft Rejection by Ex Vivo TGF-β-Induced CD4(+)Foxp3(+) Regulatory T Cells.
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体外 TGF-β 诱导的 CD4 Foxp3 调节 T 细胞对抗体介导的急性肾同种异体移植排斥的体内衰减
DOI：
10.3389/fimmu.2017.01334
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发表时间：
2017
影响因子：
7.3
通讯作者：
Sun Q
中科院分区：
文献类型：
--
作者：
Liao T;Xue Y;Zhao D;Li S;Liu M;Chen J;Brand DD;Zheng H;Zhang Y;Zheng SG;Sun Q
抗体介导的排斥反应（Antibody-mediated rejection，AMR）已成为移植肾功能不全的主要原因，需要探索更有效的策略来改善移植结局。调节性T细胞（Treg）至少由天然和诱导的Treg亚群组成，在多个水平上抑制效应子应答，并在移植耐受中发挥关键作用。在这项研究中，我们研究了诱导THBE（iTHBE）在小鼠模型中预防抗体介导的肾损伤和排斥反应的作用。我们观察到，iTdR的输注显著减轻了移植物的组织学损伤和排斥反应，并显著提高了肾移植物的存活率。iTdR显示出调节AMR中免疫紊乱的综合能力。首先，iTreg治疗降低了循环抗供体抗体的水平和同种异体移植物内的抗体沉积。第二，iT细胞显著减少细胞浸润，包括参与AMR过程的CD 4 + T细胞（包括Th 1、Th 17和Tfh）、CD 8 +IFN-γ+细胞、自然杀伤细胞、B细胞和浆细胞。我们的结果还强调了急性AMR移植物中M1巨噬细胞浸润的优势，并且iTreg治疗可以减少M1巨噬细胞。总的来说，我们的数据首次证明，TGF-β诱导的TGF-beta可以通过靶向多种效应物来减轻抗体介导的急性肾移植损伤。因此，可以预期在临床实践中使用iTdR预防AMR。
Antibody-mediated rejection (AMR) has emerged as the major cause of renal allograft dysfunction, and more effective strategies need to be explored for improving transplant outcomes. Regulatory T cells (Tregs), consisting of at least natural and induced Treg subsets, suppress effector responses at multiple levels and play a key role in transplantation tolerance. In this study, we investigated the effect of induced Tregs (iTregs) on preventing antibody-mediated renal injury and rejection in a mouse model. We observed that infusion of iTregs markedly attenuated histological graft injury and rejection and significantly improved renal allograft survival. iTregs exhibited a comprehensive ability to regulate immunological disorders in AMR. First, iTreg treatment decreased the levels of circulating antidonor antibody and the antibody deposition within allografts. Second, iTregs significantly reduced cell infiltration including CD4+ T cells (including Th1, Th17, and Tfh), CD8+IFN-γ+ cells, natural killer cells, B cells, and plasma cells, which are involved in the process of AMR. Our results also highlight a predominance of M1 macrophage infiltration in grafts with acute AMR, and M1 macrophage could be reduced by iTreg treatment. Collectively, our data demonstrate, for the first time, that TGF-β-induced Tregs can attenuate antibody-mediated acute renal allograft injury through targeting multiple effectors. Thus, use of iTregs in prevention of AMR in clinical practice could be expected.
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影响因子：
8.8
作者：
Einecke, G.;Sis, B.;Halloran, P. F.
通讯作者：
Halloran, P. F.
影响因子：
13.6
作者：
Kitching, AR;Huang, XR;Holdsworth, SR
通讯作者：
Holdsworth, SR
影响因子：
6
作者：
Bickerstaff, Alice;Pelletier, Ronald;Naclasdy, Tibor
通讯作者：
Naclasdy, Tibor
影响因子：
5.4
作者：
Hoffmann, Petra;Boeld, Tina J.;Edinger, Matthias
通讯作者：
Edinger, Matthias
DOI：
10.1111/ajt.12674
发表时间：
2014-05
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Huang G;Wilson NA;Reese SR;Jacobson LM;Zhong W;Djamali A
通讯作者：
Djamali A