小W
(2022-06-30 23:25):
#paper doi： DOI: 10.1038/s41590-022-01244-9 Glucocorticoid signaling and regulatory T cells cooperate to maintain the hair-follicle
stem-cell niche 本篇文章主要讲述利用小鼠模型研究糖皮质激素信号传导和调节性 T 细胞协同维持毛囊干细胞的生态位。在本研究中，通过特异性性敲除小鼠（GR cKO） Treg 细胞中的糖皮质激素受体 （ GR），证明GR 和 Foxp3 在 Treg 细胞中协同作用以诱导转化生长因子 β3 (TGF-β3)，从而激活 HFSCs 中的 Smad2/3 并促进 HFSC 增殖，促进毛发的再生。实验过程：在 HF 处于静止期（休止期）时去除毛干，pSmad1/5 信号通路呈阳性，48 小时内，局部皮肤中的糖皮质激素水平逐渐增加，对 PD4 天对从 GR cKO 和 WT 对照小鼠分离的 CD34+进行RNA-seq 差异基因表达和多细胞相互作用网络分析，发现Tgfβ3--Tgfbr 信号通路具有较高得分。免疫荧光和流式细胞术分析评估，Treg 细胞中 GR 的消融不会破坏脱毛后的整体皮肤免疫稳态。染色质免疫沉淀和CRISPRi系统，证实Tgfb3 和 Ttll5 的内含子区域中的 GR 和 Foxp3 结合峰是 GR 和 Foxp3 用于直接调节 Treg 细胞中 Tgfb3 表达的增强子，WT 小鼠pSmad2/3 呈阳性，确定了由 GR--TGF-β3 轴介导的 Treg 细胞和 HFSC 之间的通路。其他：1.不同组织驻留 Treg 细胞是否共享的共同调节模块2.不同浓度的糖皮质激素通过不同途径来促进和抑制斑秃
Glucocorticoid signaling and regulatory T cells cooperate to maintain the hair-follicle stem-cell niche
翻译
Abstract:
Maintenance of tissue homeostasis is dependent on the communication between stem cells and supporting cells in the same niche. Regulatory T cells (T cells) are emerging as a critical component of the stem-cell niche for supporting their differentiation. How T cells sense dynamic signals in this microenvironment and communicate with stem cells is mostly unknown. In the present study, by using hair follicles (HFs) to study T cell-stem cell crosstalk, we show an unrecognized function of the steroid hormone glucocorticoid in instructing skin-resident T cells to facilitate HF stem-cell (HFSC) activation and HF regeneration. Ablation of the glucocorticoid receptor (GR) in T cells blocks hair regeneration without affecting immune homeostasis. Mechanistically, GR and Foxp3 cooperate in T cells to induce transforming growth factor β3 (TGF-β3), which activates Smad2/3 in HFSCs and facilitates HFSC proliferation. The present study identifies crosstalk between T cells and HFSCs mediated by the GR-TGF-β3 axis, highlighting a possible means of manipulating T cells to support tissue regeneration.
翻译