Activated regulatory T cells are the major T cell type emigrating from the skin during a cutaneous immune response in mice
Activated regulatory T cells are the major T cell type emigrating from the skin during a cutaneous immune response in mice
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DOI：
10.1172/jci40926
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发表时间：
2010-03-01
影响因子：
15.9
通讯作者：
Kabashima, Kenji
中科院分区：
文献类型：
--
作者：
Tomura, Michio;Honda, Tetsuya;Kabashima, Kenji
皮肤保护剂在保护皮肤免受自身免疫攻击中起重要作用。然而，Treg在皮肤和引流淋巴结（DLN）之间运输的程度是未知的。我们着手研究这一点，使用的是表达光转换荧光蛋白Kaede的小鼠，这种蛋白在暴露于紫光时会从绿色变成红色。通过将Kaede转基因小鼠的皮肤暴露于紫光下，我们能够在生理条件下用Kaede红标记外周中的T细胞，并证明记忆表型CD 4（+）Foxp（3-）non-T细胞和CD 4（+）Foxp 3（+）T细胞在稳态下从皮肤迁移到DLN。在皮肤的免疫反应，TdR构成的主要移民和抑制免疫反应更强劲比LN居民TdR。我们一致地观察到，皮肤免疫应答通过体内内源性TdR的消耗而延长。此外，循环T细胞特异性地包括活化的CD 25（hi）T细胞，其表现出强抑制功能。总之，我们的研究结果表明，循环中的T细胞浸润外周，运输到DLN，然后再循环回到皮肤，有助于皮肤免疫反应的下调。
Tregs play an important role in protecting the skin from autoimmune attack. However, the extent of Treg trafficking between the skin and draining lymph nodes (DLNs) is unknown. We set out to investigate this using mice engineered to express the photoconvertible fluorescence protein Kaede, which changes from green to red when exposed to violet light. By exposing the skin of Kaede-transgenic mice to violet light, we were able to label T cells in the periphery under physiological conditions with Kaede-red and demonstrated that both memory phenotype CD4(+)Foxp(3-) non-Tregs and CD4(+)Foxp3(+)Tregs migrated from the skin to DLNs in the steady state. During cutaneous immune responses, Tregs constituted the major emigrants and inhibited immune responses more robustly than did LN-resident Tregs. We consistently observed that cutaneous immune responses were prolonged by depletion of endogenous Tregs in vivo. In addition, the circulating Tregs specifically included activated CD25(hi) Tregs that demonstrated a strong inhibitory function. Together, our results suggest that Tregs in circulation infiltrate the periphery, traffic to DLNs, and then recirculate back to the skin, contributing to the downregulation of cutaneous immune responses.