Glucocorticoid-induced tumor necrosis factor receptor family-related protein regulates CD4(+)T cell-mediated colitis in mice.
Glucocorticoid-induced tumor necrosis factor receptor family-related protein regulates CD4(+)T cell-mediated colitis in mice.
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DOI：
10.1053/j.gastro.2011.11.031
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发表时间：
2012-03
期刊：
影响因子：
29.4
通讯作者：
Terhorst C
中科院分区：
文献类型：
--
作者：
Liao G;Detre C;Berger SB;Engel P;de Waal Malefyt R;Herzog RW;Bhan AK;Terhorst C
糖皮质激素诱导的肿瘤坏死因子受体家族相关蛋白（GITR，也称为TNFRSF18或CD357）调节T细胞介导的免疫反应，存在于T调节性（Treg）和活化的CD4+ T细胞表面。我们研究了GITR在小鼠结肠炎发生中的作用。将野生型或GITR−/−CD4+ T细胞转移至GITR−/−xRag−/−或Rag−/−小鼠，可诱导慢性小肠结肠炎。我们使用疾病活动性指数来确定结肠炎的严重程度，测量炎症细胞因子、T细胞和树突状细胞的水平，并对结肠样本进行组织学分析。从野生型或GITR−/−供体转移未分离的CD4+细胞可诱导GITR−/−xRag−/−小鼠结肠炎，但不能诱导Rag−/−小鼠结肠炎。在转移性结肠炎小鼠中，Treg和t -辅助性（Th）17细胞的百分比降低，而Th1细胞的百分比增加。Treg细胞不能预防GITR−/−xRag−/−受体的结肠炎；这不是GITR−/−Treg或T效应细胞功能异常的结果，而是GITR−/−小鼠中耐受原性CD103+和PDCA1+浆细胞样树突状细胞数量失衡的结果。在GITR - / - xRag - / -小鼠中，非分离CD4+细胞转移后，这种不平衡损害了Treg细胞的发育，并扩大了Th1群体。诱导小鼠结肠炎不需要Treg和T效应细胞表面的GITR；结肠炎诱导不需要GITR与其配体之间的相互作用。相反，GITR似乎控制树突状细胞和单核细胞的发育；在缺乏它的情况下，小鼠通过结肠炎致Th1细胞和Treg细胞的不平衡发展为慢性小肠结肠炎。
The glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR; also called TNFRSF18 or CD357) regulates the T-cell mediated immune response and is present on surfaces of T regulatory (Treg) and activated CD4+ T cells. We investigated the roles of GITR in the development of colitis in mice. Chronic enterocolitis was induced by the transfer of wild-type or GITR−/− CD4+ T cells to GITR−/−xRag−/− or Rag−/− mice. We determined colitis severity using the disease activity index, measured levels of inflammatory cytokines, T cells, and dendritic cells, and performed histologic analysis of colon samples. Transfer of non-fractionated CD4+ cells from wild-type or GITR−/− donors induced colitis in GITR−/−xRag−/− but not in Rag−/− mice. Among mice with transfer-induced colitis, the percentage of Treg and T-helper (Th)17 cells was reduced but that of Th1 cells increased. Treg cells failed to prevent colitis in GITR−/−xRag−/− recipients; this was not the result of aberrant function of GITR−/− Treg or T effector cells, but resulted from an imbalance between the numbers of tolerogenic CD103+ and PDCA1+ plasmacytoid dendritic cells in GITR−/− mice. This imbalance impaired Treg cell development and expanded the Th1 population in GITR−/−xRag−/− mice following transfer of non-fractionated CD4+ cells. GITR is not required on the surface of Treg and T effector cells to induce colitis in mice; interactions between GITR and its ligand are not required for colitis induction. GITR instead appears to control dendritic cell and monocyte development; in its absence, mice develop aggravated chronic enterocolitis, via an imbalance of colitogenic Th1 cells and Treg cells.
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DOI：
10.1084/jem.20071160
发表时间：
2008-06-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Steinberg MW;Turovskaya O;Shaikh RB;Kim G;McCole DF;Pfeffer K;Murphy KM;Ware CF;Kronenberg M
通讯作者：
Kronenberg M
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
32.4
作者：
Siddiqui KR;Laffont S;Powrie F
通讯作者：
Powrie F
影响因子：
30.5
作者：
de Jong, YP;Abadia-Molina, AC;Terhorst, C
通讯作者：
Terhorst, C
影响因子：
4.4
作者：
POWRIE, F;LEACH, MW;COFFMAN, RL
通讯作者：
COFFMAN, RL