TIM‑4 blockade of KCs combined with exogenous TGF‑β injection helps to reverse acute rejection and prolong the survival rate of mice receiving liver allografts.
TIM‑4 blockade of KCs combined with exogenous TGF‑β injection helps to reverse acute rejection and prolong the survival rate of mice receiving liver allografts.
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TIM-4阻断KCs联合外源性TGF-注射有助于逆转急性排斥反应并延长同种异体肝移植小鼠的存活率
DOI：
10.3892/ijmm.2018.3606
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发表时间：
2018-07
影响因子：
5.4
通讯作者：
Li M
中科院分区：
文献类型：
--
作者：
Wu H;Xu X;Li J;Gong J;Li M
An acute reaction response (AR) following liver transplantation (LT) is caused by immune responses that are primarily mediated by T lymphocytes. Kupffer cells (KCs) are the largest antigen presenting cell (APC) group in vivo and are the primary modulators of the inflammatory or tolerogenic immune response in liver tissues. T cell immunoglobulin-domain and mucin-domain-4 (TIM-4), the only TIM protein not expressed on T cells, is expressed on APCs; suggesting that it mediates the various immune responses. However, to the best of our knowledge, the role of TIM-4 expressed by KCs in LT injury remains unknown. The present study aimed to explore whether and how TIM-4 expressed by KCs is involved in the AR of liver allografts. Orthotopic liver transplantation (OLT) was performed in mice to establish a model of AR and results demonstrated that LT may lead to the augmented expression of TIM-4 in activated KCs. It was also revealed that TIM-4 blockade markedly attenuated AR injury in vivo via the nuclear factor-κB (NF-κB) and p38 mitogen-activated protein kinase (p38 MAPK) signaling pathways. In addition, levels of transforming growth factor-β (TGF-β) were increased following TIM-4 blockade. Furthermore, in a KC/cluster of differentiation (CD)4+ T cell co-culture system, blocking TIM-4 inhibited T helper 2 (Th2) differentiation, stimulated the conversion of naive (CD)4+ T cells into CD4+CD25+Forkhead box protein p3+ T regulatory cells and suppressed interleukin-4/signal transducer and activator of transcription 6/transcription factor gata3 signaling. These effects were enhanced following the addition of TGF-β. It was also demonstrated that LT mouse models treated with TIM-4 blockade in combination with exogenous TGF-β injections, increased the survival times of mice and enhanced the amelioration of AR in LT. These results indicate that blocking the expression of TIM-4 by KCs via exogenous TGF-β injection may be an effective therapeutic strategy to inhibit the AR of liver allografts.
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影响因子：
4.4
作者：
Li, Pei-zhi;Li, Jin-zheng;He, Kun
通讯作者：
He, Kun
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。
影响因子：
4.4
作者：
Faust, Susan M.;Lu, Guanyi;Marini, Bernard L.;Zou, Weiping;Gordon, David;Iwakura, Yoichiro;Laouar, Yasmina;Bishop, D. Keith
通讯作者：
Bishop, D. Keith
GATA3驱动的Th2响应抑制TGF-BETA1诱导的FOXP3表达和调节T细胞的形成。
影响因子：
9.8
作者：
Mantel PY;Kuipers H;Boyman O;Rhyner C;Ouaked N;Rückert B;Karagiannidis C;Lambrecht BN;Hendriks RW;Crameri R;Akdis CA;Blaser K;Schmidt-Weber CB
通讯作者：
Schmidt-Weber CB
影响因子：
13.5
作者：
Ji, Haofeng;Liu, Yuanxing;Zhang, Yu;Shen, Xiu-da;Gao, Feng;Busuttil, Ronald W.;Kuchroo, Vijay K.;Kupiec-Weglinski, Jerzy W.
通讯作者：
Kupiec-Weglinski, Jerzy W.
影响因子：
8.7
作者：
Freeman GJ;Casasnovas JM;Umetsu DT;DeKruyff RH
通讯作者：
DeKruyff RH