Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
Graduate School of Integrated Sciences for Life, Hiroshima University, 1-4-4 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8528, Japan.
Int J Mol Sci. 2021 Jul 12;22(14):7443. doi: 10.3390/ijms22147443.
Regulatory T cells (Tregs) suppress immune responses and maintain immunological self-tolerance and homeostasis. We currently investigated relationships between skin barrier condition and Treg behavior using skin barrier-disrupted mice. Skin barrier disruption was induced by repeated topical application of 4% sodium dodecyl sulfate (SDS) on mice. The number of CD4 forkhead box protein P3 (Foxp3) Tregs was higher in 4% SDS-treated skins than in controls. This increasing was correlated with the degree of acanthosis. The numbers of interleukin (IL)-10 and transforming growth factor (TGF)-β Tregs also increased in 4% SDS-treated skins. Localization of IL-33 in keratinocytes shifted from nucleus to cytoplasm after skin barrier disruption. Notably, IL-33 promoted the migration of Tregs in chemotaxis assay. The skin infiltration of Tregs was cancelled in IL-33 neutralizing antibody-treated mice and IL-33 knockout mice. Thus, keratinocyte-derived IL-33 may induce Treg migration into barrier-disrupted skin to control the phase transition between healthy and inflammatory conditions.
调节性 T 细胞（Tregs）抑制免疫反应，维持免疫的自身耐受和体内平衡。我们目前使用皮肤屏障破坏小鼠研究了皮肤屏障状况与 Treg 行为之间的关系。通过在小鼠皮肤上反复涂抹 4%十二烷基硫酸钠（SDS）来诱导皮肤屏障破坏。与对照组相比，4% SDS 处理的皮肤中 CD4 叉头框蛋白 P3（Foxp3）Treg 的数量增加。这种增加与棘层肥厚的程度相关。IL-10 和转化生长因子（TGF）-β Tregs 的数量也在 4% SDS 处理的皮肤中增加。皮肤屏障破坏后，角质形成细胞中 IL-33 的定位从核内转移到细胞质。值得注意的是，IL-33 在趋化性测定中促进了 Treg 的迁移。在 IL-33 中和抗体处理的小鼠和 IL-33 敲除小鼠中，Treg 向皮肤的浸润被取消。因此，角质形成细胞衍生的 IL-33 可能诱导 Treg 迁移到屏障破坏的皮肤中，以控制健康和炎症状态之间的相变。
