TLR signals promote IL-6/IL-17-dependent transplant rejection.
TLR signals promote IL-6/IL-17-dependent transplant rejection.
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DOI：
10.4049/jimmunol.0803842
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发表时间：
2009-05-15
期刊：
影响因子：
--
通讯作者：
Alegre ML
中科院分区：
文献类型：
--
作者：
Chen L;Ahmed E;Wang T;Wang Y;Ochando J;Chong AS;Alegre ML
急性同种异体移植排斥反应通常与Th1分化有关，而移植耐受通常与诱导调节有关。Th17表型的发现促使其在移植排斥反应中受到密切关注。尽管最近在T-bet缺陷小鼠的急性同种异体排斥反应和驱动排斥反应中观察到了IL-17，但在野生型动物的急性排斥反应中几乎没有证据表明需要IL-17。我们和其他人之前已经证明，移植时外源性CpG发出的TLR9信号足以消除抗CD154介导的完全不相合的同种心脏移植物的接受。在这项研究中，我们研究了在这种炎症环境下发生急性排斥反应的机制。我们的结果表明，CpG以受体造血细胞为靶细胞，其促排斥作用既与阻止抗CD154介导的常规CD_4+T细胞向诱导的调节性T细胞的转化有关，也与移植物内CD_4+T细胞表达干扰素-γ和IL-17有关。此外，IL-6和IL-17信号的联合消除取消了CpG促进心脏移植急性排斥反应的能力。因此，移植时的促炎信号可以改变效应器免疫反应的质量，并揭示野生型受体对IL-6和IL-17的致病作用。
Acute allograft rejection has often been correlated with Th1 differentiation, whereas transplantation tolerance is frequently associated with induction of regulation. The discovery of the Th17 phenotype has prompted its scrutiny in transplant rejection. Although IL-17 has recently been observed in settings of acute allograft rejection and drives rejection in T-bet-deficient mice that have impaired type 1 T cell responses, there is little evidence of its requirement during acute rejection in wild-type animals. We and others have previously shown that TLR9 signaling by exogenous CpG at the time of transplantation is sufficient to abrogate anti-CD154-mediated acceptance of fully mismatched cardiac allografts. In this study, we investigated the mechanism by which acute rejection occurs in this inflammatory context. Our results indicate that CpG targets recipient hematopoietic cells and that its pro-rejection effects correlate both with prevention of anti-CD154-mediated conversion of conventional CD4+ T cells into induced regulatory T cells (iTregs) and with the expression of IFN-γ and IL-17 by intra-graft CD4+ T cells. Moreover, the combined elimination of IL-6 and IL-17 signaling abrogated the ability of CpG to promote acute cardiac allograft rejection. Thus, pro-inflammatory signals at the time of transplantation can change the quality of the effector immune response and reveal a pathogenic function for IL-6 and IL-17 in wild-type recipients.
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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
介导同种异体移植耐受性的FOXP3+ T调节细胞的募集取决于CCR4趋化因子受体。
影响因子：
15.3
作者：
Lee, I;Wang, LQ;Wells, AD;Dorf, ME;Ozkaynak, E;Hancock, WW
通讯作者：
Hancock, WW
影响因子：
32.4
作者：
Hou, Baidong;Reizis, Boris;DeFranco, Anthony L.
通讯作者：
DeFranco, Anthony L.
影响因子：
6.2
作者：
Alegre ML;Leemans J;Le Moine A;Florquin S;De Wilde V;Chong A;Goldman M
通讯作者：
Goldman M
影响因子：
56.9
作者：
Pasare, C;Medzhitov, R
通讯作者：
Medzhitov, R