Memory regulatory T cells reside in human skin
Memory regulatory T cells reside in human skin
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DOI：
10.1172/jci72932
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发表时间：
2014-03-01
影响因子：
15.9
通讯作者：
Rosenblum, Michael D.
中科院分区：
文献类型：
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作者：
Rodriguez, Robert Sanchez;Pauli, Mariela L.;Rosenblum, Michael D.
调节性T细胞(Tregs)以转录因子Foxp3的表达为特征，是一种控制免疫反应和防止自身免疫的动态异质性细胞群。我们最近在小鼠皮肤中发现了具有典型记忆细胞特性的Tregs子集，并将这一群体定义为Memory Tregs(MTregs)。由于这些细胞在调节小鼠组织炎症中的重要性，我们在人类中分析了这些细胞群，发现几乎所有正常皮肤中的Treg都具有激活的记忆表型。与外周血中的mTregs相比，皮肤mTregs具有独特的细胞表面标志物表达和细胞因子产生。在正常人皮肤中，mTregs优先定位于毛囊，且在毛发密度较高的皮肤中更为丰富。传统记忆T辅助细胞的TCR与从皮肤分离的mTregs的序列比较发现，这两个细胞群体之间几乎没有同源性，表明它们识别不同的抗原。在稳态条件下，mTregs是非迁移性的，相对没有反应；然而，在牛皮癣患者发炎的皮肤中，mTregs扩张，高度增殖，产生低水平的IL-17。综上所述，这些结果确定了稳定存在于人类皮肤中的Tregs的一个子集，并表明这些细胞在炎症性皮肤病中存在定性缺陷。
Regulatory T cells (Tregs), which are characterized by expression of the transcription factor Foxp3, are a dynamic and heterogeneous population of cells that control immune responses and prevent autoimmunity. We recently identified a subset of Tregs in murine skin with properties typical of memory cells and defined this population as memory Tregs (mTregs). Due to the importance of these cells in regulating tissue inflammation in mice, we analyzed this cell population in humans and found that almost all Tregs in normal skin had an activated memory phenotype. Compared with mTregs in peripheral blood, cutaneous mTregs had unique cell surface marker expression and cytokine production. In normal human skin, mTregs preferentially localized to hair follicles and were more abundant in skin with high hair density. Sequence comparison of TCRs from conventional memory T helper cells and mTregs isolated from skin revealed little homology between the two cell populations, suggesting that they recognize different antigens. Under steady-state conditions, mTregs were nonmigratory and relatively unresponsive; however, in inflamed skin from psoriasis patients, mTregs expanded, were highly proliferative, and produced low levels of IL-17. Taken together, these results identify a subset of Tregs that stably resides in human skin and suggest that these cells are qualitatively defective in inflammatory skin disease.