CCR10 regulates balanced maintenance and function of resident regulatory and effector T cells to promote immune homeostasis in the skin.
CCR10 regulates balanced maintenance and function of resident regulatory and effector T cells to promote immune homeostasis in the skin.
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DOI：
10.1016/j.jaci.2014.03.010
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发表时间：
2014-09
影响因子：
14.2
通讯作者：
Xiong, Na
中科院分区：
文献类型：
--
作者：
Xia, Mingcan;Hu, Shaomin;Fu, Yaoyao;Jin, Wensen;Yi, Qiyi;Matsui, Yurika;Yang, Jie;McDowell, Mary Ann;Sarkar, Surojit;Kalia, Vandana;Xiong, Na
关键词：
CCR 10和CCL 27是皮肤特异性最强的趋化因子受体/配体对，与皮肤过敏和炎症性疾病包括特应性皮炎和银屑病有关。这对被认为调节皮肤T细胞的迁移和/或维持，并被建议作为治疗皮肤疾病的治疗靶点。然而，CCR 10/CCL 27在体内的功能重要性仍然难以捉摸。我们试图确定在稳态和炎症条件下皮肤T细胞的不同亚群中CCR 10的表达和功能，以获得对CCR 10在皮肤炎症期间的潜在作用的机理性见解。使用杂合和纯合CCR 10敲除/EGFP敲入小鼠，我们评估了CCR 10在健康和炎症皮肤的调节性和效应性T细胞上的表达，这些T细胞由化学物质、病原体和自身反应性T细胞诱导。此外，我们评估了CCR 10基因敲除对免疫应答不同阶段皮肤中不同T细胞和炎症状态的维持和功能的影响。CCR 10表达优先在记忆样皮肤驻留T细胞及其祖细胞上诱导，以维持稳态皮肤，但在炎症期间在大多数皮肤浸润效应T细胞上不表达。在CCR 10基因敲除小鼠中，常驻调节和效应T细胞的不平衡存在和失调功能导致皮肤中过度反应和延长的先天和记忆反应，导致皮肤中利什曼原虫感染的清除增加。CCR 10是皮肤免疫稳态的关键调节剂。
CCR10 and CCL27 are the most skin-specific chemokine receptor/ligand pair implicated in skin allergy and inflammatory diseases including atopic dermatitis and psoriasis. This pair is thought to regulate migration and/or maintenance of skin T cells and suggested as therapeutic targets for treatment of skin diseases. However, the functional importance of CCR10/CCL27 in vivo remains elusive. We sought to determine expression and function of CCR10 in different subsets of skin T cells under both homeostatic and inflammatory conditions to gain a mechanistic insight into potential roles of CCR10 during skin inflammation. Using heterozygous and homozygous CCR10-knockout/EGFP-knockin mice, we assessed expression of CCR10 on regulatory and effector T cells of healthy and inflamed skin induced by chemicals, pathogens and auto-reactive T cells. In addition, we assessed the effect of CCR10-knockout on the maintenance and functions of different T cells and inflammatory status in the skin during different phases of the immune response. CCR10 expression is preferentially induced on memory-like skin-resident T cells and their progenitors for their maintenance in homeostatic skin but not expressed on most skin-infiltrating effector T cells during inflammation. In CCR10-knockout mice, the imbalanced presence and dysregulated function of resident regulatory and effector T cells result in over-reactive and prolonged innate and memory responses in the skin, leading to increased clearance of Leishmamia infection in the skin. CCR10 is a critical regulator of skin immune homeostasis.
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影响因子：
64.8
作者：
Rosenblum, Michael D.;Gratz, Iris K.;Paw, Jonathan S.;Lee, Karen;Marshak-Rothstein, Ann;Abbas, Abul K.
通讯作者：
Abbas, Abul K.
影响因子：
4.4
作者：
Sharma, Rahul;Sung, Sun-sang Joe;Ju, Shyr-Te
通讯作者：
Ju, Shyr-Te
影响因子：
30.5
作者：
Duhen, Thomas;Geiger, Rebekka;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
64.8
作者：
Jiang, Xiaodong;Clark, Rachael A.;Liu, Luzheng;Wagers, Amy J.;Fuhlbrigge, Robert C.;Kupper, Thomas S.
通讯作者：
Kupper, Thomas S.
DOI：
10.1084/jem.20090847
发表时间：
2009-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Francisco LM;Salinas VH;Brown KE;Vanguri VK;Freeman GJ;Kuchroo VK;Sharpe AH
通讯作者：
Sharpe AH