巨噬细胞自噬/自噬是一种细胞回收程序，以上下文相关的方式调节细胞存活和控制炎症反应。在这里，我们证明了角质细胞特异性消除自噬介导蛋白Atg16l1会导致皮肤炎症和肿瘤反应加剧。此外，缺乏角质细胞自噬的小鼠呈现出早期毛囊生长的现象，表明毛囊干细胞(HFSCs)的活化动力学发生了改变。这些HFSCs在自噬缺陷环境中也表现出扩展的潜能，如通过新生毛囊形成和改善外伤性擦伤的愈合。ATG16L1缺陷的角质细胞明显增加了凋亡的敏感性。通过RIPK3依赖性坏死性和CASP8依赖性凋亡反应的复合删除或TNFRSF1A/TNFR1的复合删除，我们发现自噬缺陷角质细胞对TNF依赖性细胞死亡的敏感性增强驱动了HFSCs的活化改变。总之，我们的数据表明，角质细胞自噬抑制了皮肤炎症和肿瘤发生，但通过抑制凋亡反应限制了HFSCs的活化。

Macroautophagy/autophagy is a cellular recycling program regulating cell survival and controlling inflammatory responses in a context-dependent manner. Here, we demonstrate that keratinocyte-selective ablation of Atg16l1, an essential autophagy mediator, results in exacerbated inflammatory and neoplastic skin responses. In addition, mice lacking keratinocyte autophagy exhibit precocious onset of hair follicle growth, indicating altered activation kinetics of hair follicle stem cells (HFSCs). These HFSCs also exhibit expanded potencies in an autophagy-deficient context as shown by de novo hair follicle formation and improved healing of abrasion wounds. ATG16L1-deficient keratinocytes are markedly sensitized to apoptosis. Compound deletion of RIPK3-dependent necroptotic and CASP8-dependent apoptotic responses or of TNFRSF1A/TNFR1 reveals that the enhanced sensitivity of autophagy-deficient keratinocytes to TNF-dependent cell death is driving altered activation of HFSCs. Together, our data demonstrate that keratinocyte autophagy dampens skin inflammation and tumorigenesis but curtails HFSC activation by restraining apoptotic responses.