title: Effects of Imiquimod on Hair Follicle Stem Cells and Hair Cycle Progression.
abstract: Topical imiquimod (IMQ) application is widely used as a model for psoriasiform-like skin inflammation in mice. Although the effects on the epidermis are well characterized, it is unclear how IMQ affects hair follicles and cycling. Here we investigated how IMQ affects hair follicle stem cells and whether the timing of IMQ application influences the immune infiltrate. Our results show that IMQ application at mid and late telogen activated hair follicle stem cells leading to premature hair cycle entry (anagen), which was accompanied by massive infiltration of inflammatory macrophages and gamma delta T cells, whereas the number of the respective resident populations decreased. Interestingly, high resident macrophage numbers were present in Rag2-/-mice and were maintained after IMQ treatment explaining why IMQ-induced anagen was reduced. This could be rescued after macrophage depletion suggesting that resident macrophages inhibit whereas inflammatory infiltrating macrophages stimulate hair follicle stem cell activation. The expression of the anagen-inhibiting factor BMP-4 was reduced by IMQ treatment as well as the activating factors Wnt showing that IMQ-induced hair follicle stem cell activation occurs by a Wnt-independent mechanism involving inflammatory cytokines such as CCL2 and TNF-α. On the basis of our findings, we recommend conducting experiments with IMQ during mid and late telogen as the biggest differences in immune cell composition are observed.
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Nicole
authors.initials: N
authors.lastname: Amberg
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Holcmann
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Stulnig
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. Electronic address: maria.sibilia@meduniwien.ac.at.
authors.forename: Maria
authors.initials: M
authors.lastname: Sibilia
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000287:Administration, Topical; D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D018859:Hair Follicle / Q000187:drug effects* / Q000473:pathology; D000077271:Imiquimod; D051379:Mice; D008810:Mice, Inbred C57BL; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D000077271:Imiquimod