Impaired autophagy promotes hair loss in the C3H/HeJ mouse model of alopecia areata

Alopecia areata (AA) involves an aberrant immune attack on the hair follicle (HF), which leads to hair loss. Previous genetic data from our lab pointed to a connection between macroautophagy/autophagy and AA pathogenesis, and GWAS identified STX17, CLEC16A and BCL2L11/BIM as risk factors for AA. Additionally, AA patients have copy number deletions in region spanning the ATG4B gene. To test whether autophagy might contribute to disease pathogenesis in AA, we investigated autophagic activity in C3H/HeJ mouse model. We found that autophagy protein SQSTM1 accumulated in HF of AA mice, while in immune cells from AA skin-draining lymph nodes SQSTM1 was not altered, suggesting that autophagic activity is inhibited in the HF of AA mice. Induction of autophagy with Tat-BECN1 peptide attenuated AA, while treatment with the autophagy blocker chloroquine promoted disease, compared to untreated AA mice. Together, our findings suggest the involvement of impaired autophagy in disease pathogenesis of AA.Abbreviations: AA: alopecia areata; CQ: chloroquine; GWAS: genome-wide association studies; HF: hair follicle; MHC: major histocompatibility complex; SDLN: skin-draining lymph nodes.