Research Center for Allergy and Immunology, RIKEN, Yokohama City, Japan.
J Clin Invest. 2010 Mar;120(3):883-93. doi: 10.1172/JCI40926. Epub 2010 Feb 22.
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+Foxp3- 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 CD25hi 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.
调节性 T 细胞(Tregs)在保护皮肤免受自身免疫攻击方面发挥着重要作用。然而,Tregs 在皮肤和引流淋巴结(DLNs)之间的迁移程度尚不清楚。我们使用表达光可转换荧光蛋白 Kaede 的转基因小鼠来研究这一问题,该蛋白在暴露于紫光时会从绿色变为红色。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-red 标记外周血中的 T 细胞,并证明记忆表型 CD4+Foxp3-非 Tregs 和 CD4+Foxp3+ Tregs 均从皮肤迁移到稳定状态下的 DLNs。在皮肤免疫反应中,Tregs 是主要的迁出细胞,并且比 LN 驻留的 Tregs 更能抑制免疫反应。我们一致观察到,体内耗尽内源性 Tregs 会延长皮肤免疫反应。此外,循环 Tregs 特别包括具有强抑制功能的活化 CD25hi Tregs。综上所述,我们的结果表明,循环中的 Tregs 浸润外周,迁移到 DLNs,然后再循环回到皮肤,有助于下调皮肤免疫反应。
J Clin Invest. 2010-2-22
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