JAK-STAT1 as therapeutic target for EGFR deficiency-associated inflammation and scarring alopecia

ABSTRACT: The hair follicle stem cell niche is an immune-privileged microenvironment, characterized by reduced antigen presentation, thus shielding against permanent immune-mediated tissue damage. In this study, we demonstrated the protective role of hair follicle-specific epidermal growth factor receptor (EGFR) against scarring hair follicle destruction. Mechanistically, disruption of EGFR signalling generated a cell-intrinsic hypersensitivity within the JAK-STAT1 pathway, which, synergistically with interferon gamma expressing CD8 T-cell and NK-cell-mediated inflammation, compromised the stem cell niche. Hair follicle-specific genetic depletion of either JAK1/2 or STAT1 or therapeutic inhibition of JAK1/2 ameliorated the inflammation, restored skin barrier function and activated the residual stem

SUBMITTER: Dr. Karoline Strobl 

PROVIDER: S-SCDT-10_1038-S44321-024-00166-3 | biostudies-other |

REPOSITORIES: biostudies-other