The Involvement of RIPK1 in Alopecia Areata

We previously identified receptor-interacting serine/threonine kinase 1 (RIPK1) as a key regulator of the hair cycle, with expression localized to hair follicles. In mouse models, pharmacological inhibition of RIPK1 promoted the transition from telogen to anagen and prolonged the anagen phase. In the present study, we explored the role of RIPK1 in alopecia areata (AA). Both mRNA and protein levels of RIPK1 were elevated in the skin of an AA mouse model. Single-cell RNA sequencing and immunohistochemistry revealed marked upregulation of RIPK1 in dendritic cells (DCs) and CD8+ T cells. Treatment with RIPK1 inhibitors (Necrostatin-1s and GSK2982772) delayed AA onset and reduced the accumulation of DCs and CD8+ T cells in the affected skin. Furthermore, RIPK1 inhibition increased hair shaft length in an ex vivo hair organ culture model of AA. Taken together, these findings indicate that RIPK1 contributes to AA pathogenesis by modulating immune cell activity, and that RIPK1 inhibitors may offer therapeutic potential for AA prevention.