| First Author | Van Hove L | Year | 2023 |
| Journal | Autophagy | Volume | 19 |
| Issue | 11 | Pages | 2958-2971 |
| PubMed ID | 37615626 | Mgi Jnum | J:340877 |
| Mgi Id | MGI:7531246 | Doi | 10.1080/15548627.2023.2247742 |
| Citation | Van Hove L, et al. (2023) Autophagy critically controls skin inflammation and apoptosis-induced stem cell activation. Autophagy :1-14 |
| abstractText | 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. |
