Regulatory T cells in skin mediate immune privilege of the hair follicle stem cell niche.
Regulatory T cells in skin mediate immune privilege of the hair follicle stem cell niche.
复制标题
皮肤中的调节性 T 细胞介导毛囊干细胞生态位的免疫特权。
DOI：
10.1126/sciimmunol.adh0152
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发表时间：
2024
影响因子：
24.8
通讯作者：
Rosenblum,MichaelD
中科院分区：
文献类型：
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作者：
Cohen,JarishN;Gouirand,Victoire;Macon,CourtneyE;Lowe,MargaretM;Boothby,IanC;Moreau,JoshuaM;Gratz,IrisK;Stoecklinger,Angelika;Weaver,CaseyT;Sharpe,ArleneH;Ricardo-Gonzalez,RobertoR;Rosenblum,MichaelD
免疫耐受在淋巴器官（LO）中维持。尽管在非LO中存在复杂的免疫细胞网络，但尚不清楚这些组织中是否维持了自身耐受性。我们开发了一种技术，以限制基因重组的调节性T细胞（T细胞）只在皮肤中。皮肤Tregs的选择性耗竭导致T细胞介导的毛囊（HF）炎症。抑制并不依赖于CTLA-4，而是依赖于皮肤T细胞表达的高亲和力白细胞介素-2（IL-2）受体，仅以细胞外源性方式发挥作用。在HF干细胞（HFSC）驱动的自身免疫的新模型中，我们揭示了皮肤Treg免疫保护HFSC生态位。最后，我们使用空间转录组学来鉴定以HFSC破坏和斑秃为特征的罕见人类脱发中基质-HF界面的异常IL-2信号传导。总的来说，这些结果揭示了Tregsin皮肤与全身性库解偶联的基本生物学，并阐明了自身耐受性的机制。
Immune tolerance is maintained in lymphoid organs (LOs). Despite the presence of complex immune cell networks in non-LOs, it is unknown whether self-tolerance is maintained in these tissues. We developed a technique to restrict genetic recombination to regulatory T cells (Tregs) only in skin. Selective depletion of skin Tregsresulted in T cell–mediated inflammation of hair follicles (HFs). Suppression did not rely on CTLA-4, but instead on high-affinity interleukin-2 (IL-2) receptor expression by skin Tregs, functioning exclusively in a cell-extrinsic manner. In a novel model of HF stem cell (HFSC)–driven autoimmunity, we reveal that skin Tregsimmunologically protect the HFSC niche. Finally, we used spatial transcriptomics to identify aberrant IL-2 signaling at stromal-HF interfaces in a rare form of human alopecia characterized by HFSC destruction and alopecia areata. Collectively, these results reveal the fundamental biology of Tregsin skin uncoupled from the systemic pool and elucidate a mechanism of self-tolerance.