Anti-IL-17 therapy restricts and reverses late-term corneal allorejection.
Anti-IL-17 therapy restricts and reverses late-term corneal allorejection.
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DOI：
10.4049/jimmunol.1401922
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发表时间：
2015-04-15
期刊：
影响因子：
--
通讯作者：
Stuart PM
中科院分区：
文献类型：
--
作者：
Yin XT;Zobell S;Jarosz JG;Stuart PM
角膜同种异体移植排斥被描述为涉及 IFN-γ 产生的 Th1 介导过程。然而，最近的证据也表明 IL-17 参与急性角膜同种异体移植反应。我们的数据支持那些认为 IL-17 参与早期急性角膜同种异体移植接受的观点。然而，我们决定将这些研究扩展到包括排斥的后期阶段，其中 IL-17 产生的峰值比急性排斥期间的峰值高 15 倍以上，急性排斥发生在植入后 45 天以上，即晚期排斥开始时。我们证明此时中和 IL-17A 可显着减少角膜移植排斥。令人惊讶的是，当正在经历排斥反应后期的角膜移植物用抗IL17A治疗时，混浊和新血管形成都出现逆转。与排斥早期相比，细胞浸润明显减少，Gr-1+ 中性粒细胞大大减少，CD4+ T 细胞和巨噬细胞相对增加。我们继续鉴定出表达 IL-17 的细胞是 CD4+ IL-17+ T 细胞，令人惊讶的是，排斥性角膜同种异体移植物中表达 IL-17+ F4/80+ 巨噬细胞。总而言之，这些发现描述了角膜同种异体移植排斥的明显晚期阶段，这可能是由 Th17 细胞介导的，并且 IL-17A 的治疗中和可逆转这种排斥。这进一步表明 IL-17 可能作为减少这种形式的角膜同种异体移植排斥的绝佳治疗靶点。
Corneal allograft rejection has been described as a Th1-mediated process involving IFN-γ production. However, recent evidence has also implicated IL-17 as being involved during acute corneal allograft responses. Our data supports those that maintain that IL-17 is involved in early acute corneal allograft acceptance. However, we decided to extend these studies to include a later phase of rejection in which there is a peak of IL-17 production that is >15 fold higher than seen during acute rejection that occurs >45 days post-engraftment at the onset of late-term rejection. We demonstrate that neutralizing IL-17A at this time significantly reduced corneal graft rejection. Surprisingly, when corneal grafts that are undergoing this later phase of rejection are treated with anti-IL17A there is a reversal of both opacity and neovascularization. When compared to the early phase of rejection, the cellular infiltrate is significantly less with a greatly reduced presence of Gr-1+ neutrophils with a relative increase in CD4+ T cells and macrophages. We went on to identify that the cells expressing IL-17 were CD4+ IL-17+ T cells and somewhat surprisingly, IL-17+ F4/80+ macrophages within the rejecting corneal allografts. Taken together, these findings describe a distinct late phase of corneal allograft rejection which is likely mediated by Th17 cells and that therapeutic neutralization of IL-17A reverses this rejection. This further suggests that IL-17 might serve as an excellent therapeutic target to reduce this form of corneal allograft rejection.
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DOI：
10.1084/jem.20071507
发表时间：
2008-02-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Pichavant M;Goya S;Meyer EH;Johnston RA;Kim HY;Matangkasombut P;Zhu M;Iwakura Y;Savage PB;DeKruyff RH;Shore SA;Umetsu DT
通讯作者：
Umetsu DT
影响因子：
13.7
作者：
Ing, JJ;Ing, HH;Bourne, WM
通讯作者：
Bourne, WM
影响因子：
6
作者：
Katsifis, Gikas E.;Rekka, Sofia;Wahl, Sharon M.
通讯作者：
Wahl, Sharon M.
影响因子：
0.9
作者：
Liu, X. C.;Zhai, A.;Qi, H. Z.
通讯作者：
Qi, H. Z.
影响因子：
1.5
作者：
Chen, Haiyong;Wang, Weilin;Zheng, Shusen
通讯作者：
Zheng, Shusen