Role of T cell TGFbeta signaling and IL-17 in allograft acceptance and fibrosis associated with chronic rejection.
Role of T cell TGFbeta signaling and IL-17 in allograft acceptance and fibrosis associated with chronic rejection.
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T 细胞 TGFbeta 信号传导和 IL-17 在同种异体移植接受和慢性排斥相关纤维化中的作用。
DOI：
10.4049/jimmunol.0902446
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发表时间：
2009-12-01
影响因子：
4.4
通讯作者：
Bishop, D. Keith
中科院分区：
文献类型：
--
作者：
Faust, Susan M.;Lu, Guanyi;Marini, Bernard L.;Zou, Weiping;Gordon, David;Iwakura, Yoichiro;Laouar, Yasmina;Bishop, D. Keith
慢性同种异体移植排斥反应（CR）是影响移植物长期存活的主要障碍。CR是一种进行性疾病，定义为间质纤维化、血管新生内膜发展和移植物功能障碍。导致CR的潜在机制仍不清楚。转化生长因子β（TGFβ）与促进纤维化疾病（包括CR）有关，但由于其免疫抑制活性，在移植环境中是有益的。为了评估T细胞TGFβ信号传导在同种异体移植物接受和CR进展中的需要，我们使用具有废除的T细胞TGFβ信号传导的小鼠作为同种异体移植物接受者。我们比较了CD 4+细胞瞬时耗竭（发生CR并表达移植物内TGFβ）的受体的反应与接受抗CD 40 L mAb治疗（不发生CR且不表达移植物内TGFβ）的小鼠的反应。在用抗CD 40 L mAb处理的小鼠中，同种异体移植物接受和移植物反应性T和B细胞的抑制不依赖于T细胞TGFβ信号传导。在CD 4 + T细胞短暂耗竭的受体中，T细胞TGFβ信号传导是与CR相关的纤维化、长期移植物接受以及移植物反应性T和B细胞应答抑制的发展所必需的。此外，IL-17被鉴定为TGFβ驱动的同种异体移植物纤维化中的关键因素。因此，IL-17可以提供用于预防移植物纤维化的治疗靶标，这是CR的量度，同时保留TGFβ的免疫抑制活性。
Chronic allograft rejection (CR) is the main barrier to long-term transplant survival. CR is a progressive disease defined by interstitial fibrosis, vascular neointimal development, and graft dysfunction. The underlying mechanisms responsible for CR remain poorly defined. Transforming growth factor β (TGFβ) has been implicated in promoting fibrotic diseases including CR, but is beneficial in the transplant setting due to its immunosuppressive activities. To assess the requirement for T cell TGFβ signaling in allograft acceptance and the progression of CR, we used mice with abrogated T cell TGFβ signaling as allograft recipients. We compared responses from recipients that were transiently depleted of CD4+ cells (that develop CR and express intragraft TGFβ) to responses from mice that received anti-CD40L mAb therapy (that do not develop CR and do not express intragraft TGFβ). Allograft acceptance and suppression of graft-reactive T and B cells were independent of T cell TGFβ signaling in mice treated with anti-CD40L mAb. In recipients transiently depleted of CD4+ T cells, T cell TGFβ signaling was required for the development of fibrosis associated with CR, long-term graft acceptance, and suppression of graft-reactive T and B cell responses. Further, IL-17 was identified as a critical element in TGFβ driven allograft fibrosis. Thus, IL-17 may provide a therapeutic target for preventing graft fibrosis, a measure of CR, while sparing the immunosuppressive activities of TGFβ.
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影响因子：
4.4
作者：
Bestard, Oriol;Cruzado, Josep M.;Grinyo, Josep M.
通讯作者：
Grinyo, Josep M.
影响因子：
6.2
作者：
Chan, SY;Goodman, RE;Bishop, DK
通讯作者：
Bishop, DK
DOI：
10.1152/ajpheart.00928.2007
发表时间：
2007-12-01
影响因子：
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作者：
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通讯作者：
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影响因子：
8.8
作者：
Csencsits, K.;Burrell, B. E.;Bishop, D. K.
通讯作者：
Bishop, D. K.
影响因子：
8.8
作者：
Csencsits, K;Wood, SC;Bishop, DK
通讯作者：
Bishop, DK