829 Cytotoxic T lymphocytes target henle’s layer in alopecia areata

Autoimmune disease occurs when a specific adaptive immune response is mounted against self-antigen(s) and immune-mediated tissue damage sustained until the self-antigen eliminated. We recently identified immunogenic cell death via necroptosis in hair follicle (HF) epithelium as primary initiating mechanism alopecia areata (AA). Here, we aimed to identify major target cells of T cell-mediated cytotoxicity AA, after autoimmune was initiated. Using C3H/HeJ mouse model first established spatiotemporal map caspase-8-driven apoptosis HF epithelial during premature regression AA. found that c-caspase-8+ apoptotic were selectively localized within Henle’s layer, outermost Krt71+ layer inner root sheath (IRS), but not outer or matrix region. previously reported also showed high expression H60, ligand for NKG2D receptor expressed on CD8+ cells. Similarly, lesional scalp AA patients, located KRT71+ IRS which ULBP2/5/6, human ligands receptor. The Krt71 extended up lower half anagen, therefore defined anatomical zone infiltration limited area bulb region HF. Interestingly, occasionally residual expressing tissue-resident memory (Trm) markers infundibulum isthmus regions telogen HFs. persistence Trm population HFs suggests these may participate re-initiation subsequent cycle. Our study autoreactive attack provides mechanistic explanation why anagen