Effects of Imiquimod on Hair Follicle Stem Cells and Hair Cycle Progression

The study investigated the effects of topical imiquimod (IMQ) on hair follicle stem cells and hair cycle progression in mice. The researchers found that applying IMQ during the mid and late stages of the resting phase (telogen) of the hair cycle activated hair follicle stem cells, causing premature entry into the growth phase (anagen). This activation was associated with a significant increase in inflammatory macrophages and gamma delta T cells, while the number of resident immune cells decreased. In Rag2-/- mice, which have high numbers of resident macrophages, IMQ-induced anagen was reduced, but this effect was reversed after depleting macrophages, indicating that resident macrophages inhibit hair follicle stem cell activation, whereas infiltrating macrophages stimulate it. IMQ treatment also decreased the expression of the anagen-inhibiting factor BMP-4 and altered the expression of Wnt, suggesting that IMQ-induced hair follicle stem cell activation is mediated by a Wnt-independent mechanism involving inflammatory cytokines like CCL2 and TNF-α. The study recommends using IMQ during mid and late telogen for experiments due to the pronounced differences in immune cell composition observed.