CCR4 and CXCR3 play different roles in the migration of T cells to inflammation in skin, arthritic joints, and lymph nodes
CCR4 and CXCR3 play different roles in the migration of T cells to inflammation in skin, arthritic joints, and lymph nodes
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DOI：
10.1002/eji.201343995
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发表时间：
2014-06-01
影响因子：
5.4
通讯作者：
Issekutz, Thomas B.
中科院分区：
文献类型：
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作者：
Al-Banna, Nadia A.;Vaci, Maria;Issekutz, Thomas B.
CCR 4和CXCR 3在炎症组织中的几个T细胞亚群上表达，但它们在组织特异性募集中的作用尚不清楚。我们使用来自CXCR 3-/-、CCR 4-/-和WT小鼠的标记活化T细胞，检测了CCR 4和CXCR 3对胶原诱导的关节炎、抗原引流淋巴结（LN）和皮肤炎症部位（聚I：C、LPS、伴刀豆球蛋白A和迟发型超敏反应）炎症关节中T细胞募集的贡献。CXCR 3和CCR 4缺乏都减少了关节炎的发展，但不影响Th 1细胞向发炎关节的募集。炎症LN中的蓄积高度依赖CXCR 3。相反，CCR 4缺陷型Th 1细胞在这些LN中的积累增加。活化的Th 1和T细胞毒性细胞和记忆性CD 4 + T细胞迁移到所有四个皮肤炎症部位部分依赖于CXCR 3，但Treg细胞迁移不依赖于CXCR 3。表达CCR 4的细胞亚群具有皮肤迁移特性，但CCR 4本身不是迁移所必需的。因此，向这些发炎组织的迁移是不依赖于CCR 4的，并且部分依赖于CXCR 3，除了Treg细胞，其不需要受体。因此，CCR 4可能影响T细胞在不同组织中的保留，而不是从血液中运输出来。
CCR4 and CXCR3 are expressed on several T-cell subsets in inflamed tissues, yet their role in tissue-specific recruitment is unclear. We examined the contributions of CCR4 and CXCR3 to T-cell recruitment into inflamed joints in collagen-induced arthritis, antigen-draining lymph nodes (LNs) and dermal inflammatory sites (poly I:C, LPS, concanavalin A, and delayed type hypersensitivity), using labeled activated T cells from CXCR3-/-, CCR4-/-, and WT mice. Both CXCR3 and CCR4 deficiency reduced the development of arthritis, but did not affect Th1-cell recruitment to the inflamed joints. Accumulation in inflamed LNs was highly CXCR3 dependent. In contrast, CCR4-deficient Th1 cells had an increased accumulation in these LNs. Migration to all four dermal inflammatory sites by activated Th1 and T cytotoxic cells and memory CD4+ T cells was partially CXCR3-dependent, but Treg-cell migration was independent of CXCR3. The subset of cells expressing CCR4 has skin-migrating properties, but CCR4 itself is not required for the migration. Thus, migration into these inflamed tissues is CCR4-independent, and partially dependent on CXCR3, except for Treg cells, which require neither receptor. CCR4 may therefore affect retention of T cells in different tissues rather than trafficking out of the blood.