Glucocorticoid-induced TNF receptor family- related protein ligand regulates the migration of monocytes to the inflamed intestine
Glucocorticoid-induced TNF receptor family- related protein ligand regulates the migration of monocytes to the inflamed intestine
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DOI：
10.1096/fj.13-236505
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发表时间：
2014-01-01
期刊：
影响因子：
4.8
通讯作者：
Terhorst, Cox
中科院分区：
文献类型：
--
作者：
Liao, Gongxian;van Driel, Boaz;Terhorst, Cox
糖皮质激素诱导的TNF受体家族相关蛋白（GITR）调节T细胞和抗原呈递细胞（APCs）的功能，而GITR配体（GITR- l）的功能在很大程度上是未知的。GITR-L的表达仅限于apc，我们在此评估GITR-L在小肠结肠炎发展中的作用。注射初始CD4(+) T细胞后，GITR-L(-/-)Rag（-/-）小鼠结肠炎明显轻于Rag（-/-）小鼠，这与固有层和肠系膜淋巴结中Ly6C(+)CD11b(+)MHCII（+）巨噬细胞减少50%相关。在cd40诱导的急性结肠炎和腹膜炎中也观察到同样的结果，表明单核细胞迁移发生了改变。与这些观察结果一致，CD40诱导后，GITR-L(-/-)Rag（-/-）小鼠脾脏中未分化单核细胞的数量比Rag（-/-）小鼠脾脏中未分化单核细胞的数量高出约3倍。与肠道炎症期间GITR-L-/-脾脏单核细胞中活性血管紧张素II型1受体（AT1）二聚体形成的动态变化一致，GITR-L-缺陷小鼠脾脏单核细胞的迁移能力在体外跨井迁移实验中受到损害。相反，GITR-L减少脾脏Ly6C（hi）单核细胞的数量，同时增加AT1二聚体。我们得出结论，GITR-L通过控制脾库中单核细胞的输出来调节炎症部位的促炎巨噬细胞的数量。Liao， G., van Driel， B., Magelky， E.， O'Keeffe， M. S., de Waal Malefyt， R., Engel， P., Herzog， R. W., Mizoguchi， E., Bhan， A. K., Terhorst， C.糖皮质激素诱导的TNF受体家族相关蛋白配体调节单核细胞向炎症肠道的迁移。
Glucocorticoid-induced TNF receptor family-related protein (GITR) regulates the function of both T cells and antigen-presenting cells (APCs), while the function of GITR ligand (GITR-L) is largely unknown. Here we evaluate the role of GITR-L, whose expression is restricted to APCs, in the development of enterocolitis. On injecting naive CD4(+) T cells, GITR-L(-/-)Rag(-/-) mice develop a markedly milder colitis than Rag(-/-) mice, which correlates with a 50% reduction of Ly6C(+)CD11b(+)MHCII(+) macrophages in the lamina propria and mesenteric lymph nodes. The same result was observed in CD40-induced acute colitis and during peritonitis, suggesting an altered monocyte migration. In line with these observations, the number of nondifferentiated monocytes was approximately 3-fold higher in the spleen of GITR-L(-/-)Rag(-/-) mice than in Rag(-/-) mice after CD40 induction. Consistent with the dynamic change in the formation of an active angiotensin II type 1 receptor (AT1) dimer in GITR-L-/- splenic monocytes during intestinal inflammation, the migratory capability of splenic monocytes from GITR-L-deficient mice was impaired in an in vitro transwell migration assay. Conversely, GITR-L reduces the number of splenic Ly6C(hi) monocytes, concomitantly with an increase in AT1 dimers. We conclude that GITR-L regulates the number of proinflammatory macrophages in sites of inflammation by controlling the egress of monocytes from the splenic reservoir.Liao, G., van Driel, B., Magelky, E., O'Keeffe, M. S., de Waal Malefyt, R., Engel, P., Herzog, R. W., Mizoguchi, E., Bhan, A. K., Terhorst, C. Glucocorticoid-induced TNF receptor family-related protein ligand regulates the migration of monocytes to the inflamed intestine.