Epidermal RANKL controls regulatory T-cell numbers via activation of dendritic cells
Epidermal RANKL controls regulatory T-cell numbers via activation of dendritic cells
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DOI：
10.1038/nm1518
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发表时间：
2006-12-01
期刊：
影响因子：
82.9
通讯作者：
Beissert, Stefan
中科院分区：
文献类型：
--
作者：
Loser, Karin;Mehling, Annette;Beissert, Stefan
调节性CD 4（+）CD 25（+）T细胞在抑制免疫应答中很重要。维持外周血CD 4（+）CD 25（+）T细胞的需要仍然不完全清楚。NF-κ B受体激活剂（RANK）及其配体（RANKL;也称为CD 254、OPGL和TRANCE）是骨重塑、乳腺形成、淋巴结发育和T细胞/树突状细胞通讯的关键调节因子。在这里，我们报告说，RANKL表达在角质形成细胞的发炎的皮肤。角质形成细胞中RANKL过表达导致表皮树突状细胞的功能改变和调节性CD 4（+）CD 25（+）T细胞的系统性增加。因此，表皮RANKL表达可以改变树突状细胞的功能，以维持外周CD 4（+）CD 25（+）调节性T细胞的数量。表皮RANKL介导的紫外线诱导的免疫抑制和表皮RANKL的过表达可抑制过敏性接触性超敏反应和全身性自身免疫的发生。因此，皮肤的环境刺激可以通过RANKL重新连接局部和全身免疫系统。
Regulatory CD4(+)CD25(+) T cells are important in suppressing immune responses. The requirements for the maintenance of peripheral CD4(+)CD25(+) T cells remain incompletely understood. Receptor activator of NF-kappa B ( RANK) and its ligand (RANKL; also known as CD254, OPGL and TRANCE) are key regulators of bone remodeling, mammary gland formation, lymph node development and T-cell/dendritic cell communication. Here we report that RANKL is expressed in keratinocytes of the inflamed skin. RANKL overexpression in keratinocytes resulted in functional alterations of epidermal dendritic cells and systemic increases of regulatory CD4(+)CD25(+) T cells. Thus, epidermal RANKL expression can change dendritic cell functions to maintain the number of peripheral CD4(+)CD25(+) regulatory T cells. Epidermal RANKL mediated ultraviolet-induced immunosuppression and overexpression of epidermal RANKL suppressed allergic contact hypersensitivity responses and the development of systemic autoimmunity. Therefore, environmental stimuli at the skin can rewire the local and systemic immune system by means of RANKL.