An Emerging Role of TIM3 Expression on T Cells in Chronic Kidney Inflammation.
An Emerging Role of TIM3 Expression on T Cells in Chronic Kidney Inflammation.
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T 细胞 TIM3 表达在慢性肾脏炎症中的新作用
DOI：
10.3389/fimmu.2021.798683
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发表时间：
2021
影响因子：
7.3
通讯作者：
Chen G
中科院分区：
文献类型：
--
作者：
Lu C;Chen H;Wang C;Yang F;Li J;Liu H;Chen G
T细胞免疫球蛋白结构域和粘蛋白结构域3（TIM 3）最初被鉴定为对产生IFNγ的T细胞的抑制性分子。进一步的研究发现TIM3在不同的免疫细胞上广泛表达，与多种配体结合。除了其对Th1细胞的抑制作用外，最近令人信服的实验强调了TIM 3在骨髓细胞介导的炎症反应中不可或缺的作用，支持TIM 3以上下文依赖的方式对适应性和先天性免疫细胞发挥多效性作用。已经在感染、癌症和自身免疫的疾病环境中对TIM3生物学进行了大量研究。然而，缺乏临床证据来密切评估T细胞表达TIM3在慢性肾脏病（CKD）发病机制中的作用。在这里，我们报告了一个有趣的结核分枝杆菌（Mtb）感染的情况下，其特征是持续过度表达的TIM3循环T细胞和持续的肾小管间质炎症，为期12个月。在这种情况下，多个组织病理学活检显示，在扩大的肾脏和肝脏中大量积累了募集的T细胞和巨噬细胞。标准抗结核治疗后，反复肾活检发现肾小管间质室中浸润的免疫细胞显著缓解。这是第一个揭示T细胞上TIM3的时程表达的临床报告，其在非自身免疫性环境中与严重肾脏炎症的进展病理相关。基于这种情况下，我们总结了TIM3生物学的最新研究结果，并提出了一种新的模型，CKD的进展，由于免疫细胞之间的异常串扰。
T cell immunoglobulin domain and mucin domain 3 (TIM3) was initially identified as an inhibitory molecule on IFNγ-producing T cells. Further research discovered the broad expression of TIM3 on different immune cells binding to multiple ligands. Apart from its suppressive effects on the Th1 cells, recent compelling experiments highlighted the indispensable role of TIM3 in the myeloid cell-mediated inflammatory response, supporting that TIM3 exerts pleiotropic effects on both adaptive and innate immune cells in a context-dependent manner. A large number of studies have been conducted on TIM3 biology in the disease settings of infection, cancer, and autoimmunity. However, there is a lack of clinical evidence to closely evaluate the role of T cell-expressing TIM3 in the pathogenesis of chronic kidney disease (CKD). Here, we reported an intriguing case of Mycobacterium tuberculosis (Mtb) infection that was characterized by persistent overexpression of TIM3 on circulating T cells and ongoing kidney tubulointerstitial inflammation for a period of 12 months. In this case, multiple histopathological biopsies revealed a massive accumulation of recruited T cells and macrophages in the enlarged kidney and liver. After standard anti-Mtb treatment, repeated renal biopsy identified a dramatic remission of the infiltrated immune cells in the tubulointerstitial compartment. This is the first clinical report to reveal a time-course expression of TIM3 on the T cells, which is pathologically associated with the progression of severe kidney inflammation in a non-autoimmunity setting. Based on this case, we summarize the recent findings on TIM3 biology and propose a novel model of CKD progression due to the aberrant crosstalk among immune cells.
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影响因子：
6.7
作者：
Croft NP;Smith SA;Wong YC;Tan CT;Dudek NL;Flesch IE;Lin LC;Tscharke DC;Purcell AW
通讯作者：
Purcell AW
影响因子：
30.5
作者：
Chiba, Shigeki;Baghdadi, Muhammad;Akiba, Hisaya;Yoshiyama, Hironori;Kinoshita, Ichiro;Dosaka-Akita, Hirotoshi;Fujioka, Yoichiro;Ohba, Yusuke;Gorman, Jacob V.;Colgan, John D.;Hirashima, Mitsuomi;Uede, Toshimitsu;Takaoka, Akinori;Yagita, Hideo;Jinushi, Masahisa
通讯作者：
Jinushi, Masahisa
影响因子：
4.6
作者：
Guo, Ling;Yang, Xiangdong;Peng, Tao
通讯作者：
Peng, Tao
影响因子：
8.7
作者：
Freeman GJ;Casasnovas JM;Umetsu DT;DeKruyff RH
通讯作者：
DeKruyff RH
影响因子：
20.3
作者：
Elahi, Shokrollah;Niki, Toshiro;Horton, Helen
通讯作者：
Horton, Helen