Interferon-γ is a potent inducer of catagen-like changes in cultured human anagen hair follicles

Background: Interferon (IFN)-γ appears to be an important hair cycle modulator in mice. It is unclear whether it has similar hair growth modulatory functions in human hair follicles. Objectives: To study whether IFN-γ can be exploited to modulate the growth, pigmentation and/or cycling of organ-cultured human anagen scalp hair follicles, as an in vitro indicator system for how IFN-γ affects human hair growth in vivo. This was correlated with the hair follicle expression patterns of IFN-γ receptors α and β. In addition, we wanted to establish a new, simple tool for the rapid experimental induction of catagen in vitro. Methods: Normal human scalp hair follicles in the anagen VI stage of the hair cycle were cultured according to the method of Philpott et al., with or without IFN-γ (50-1000 IU mL^-1). Hair shaft elongation and pigmentation changes were measured, complemented by quantitative histomorphometry to assess changes in hair follicle cycling (hair cycle score), proliferation (Ki-67), melanogenesis (Masson-Fontana) and apoptosis (TUNEL). IFN-γ receptors were also localized by immunofluorescence and EnVision technique. As transforming growth factor (TGF)-β2 is a recognized key inducer of catagen in human hair follicles, TGF-β2 expression was investigated by tyramide signal amplification and reverse transcription-polymerase chain reaction in anagen hair follicles treated with vehicle (phosphate-buffered saline) or IFN-γ. Results: IFN-γ rapidly inhibited hair elongation in cultured human anagen hair follicles and induced morphological signs of catagen transformation after only 4 days of culture, i.e. faster than with other reported catagen-inducers (e.g. TGF-β2). Proliferation was inhibited, apoptosis was increased and follicular melanogenesis was switched off in hair bulb keratinocytes treated in situ with IFN-γ. Anagen hair follicles displayed strong IFN-γ receptor α-like immunoreactivity, while the immunoreactivity for IFN-γ receptor β in the hair matrix was only weak. TGF-β2 immunoreactivity and mRNA transcript levels were enhanced in hair follicles treated with IFN-γ. Conclusions: These data-suggest that IFN-γ is a potent catagen inducer in normal human scalp hair follicles, which express cognate receptors, and show that IFN-γ administration offers an excellent tool for experimental catagen induction in organ-cultured human hair follicles. This catagen induction probably occurs at least in part via upregulation of the recognized catagen-stimulatory growth factor TGF-β2.