Hair growth control by innate immunocytes: Perifollicular macrophages revisited

Abstract

The role of innate immunocytes such as mast cells, γδ T cells, NK cells and macrophages (MACs) in hair growth control under physiological and pathological conditions has recently begun to be re‐explored. Here, we revisit the role of resident perifollicular macrophages (pfMACs) located in the hair follicle (HF) mesenchyme (CTS). Substantial, stringently timed fluctuations in the number and localization of pfMACs were first observed long ago during murine HF morphogenesis and cycling. This already suggested some involvement of these innate immunocytes, with a recognized role in tissue remodelling and in hair growth control. The relatively recent demonstration of a Wnt signalling‐driven crosstalk between these immunocytes and HF epithelial stem cells in telogen HFs, which promotes anagen induction, has reinvigorated interest in the role that pfMAC plays in hair biology. Besides the apoptosis‐associated secretion of stem cell–activating Wnts and the differential secretion of HF‐targeting growth factors such as FGF‐5 and FGF5s from pfMACs, we also explore how MAC polarization, and thus function, may be influenced by the local metabolic and immune environment. Moreover, we examine how pfMACs may contribute to hair cycle–associated angiogenesis, vascular remodelling, HF immune privilege and immunopathology. On this basis, we discuss why targeting pfMACs may be relevant in the management of hair growth disorders. Finally, we argue that studying pfMACs offers an excellent, clinically relevant model system for characterizing and experimentally manipulating MAC interactions with an easily accessible mammalian, continuously remodelled (mini‐)organ under both physiological and pathological conditions.

Immune cell regulation of the hair cycle

“…The HF epithelium is also densely populated by DETCs in both mice and humans . Likewise, dermal macrophages are found to be associated with almost every stage of the hair cycle and may play multiple roles in the maintenance of the HF.…”

New developments in hair research

“…[34] Perifollicular mast cells, γδ T cells, natural killer cells and macrophages are understood to affect hair growth cycles via secretion of hair follicle-targeting growth factors. [35] Interestingly, recent studies suggest another mode of action by which cells may signal to each other. Exosomes derived from cultured dermal papilla cells could be used to induce trichogenicity of dermal papilla cells in a hair reconstitution assay.…”

“…Wang and Higgins review the evidence to date and consider the mechanisms of immune cell influence over hair growth and hair loss . Perifollicular mast cells, γδ T cells, natural killer cells and macrophages are understood to affect hair growth cycles via secretion of hair follicle‐targeting growth factors . Interestingly, recent studies suggest another mode of action by which cells may signal to each other.…”

Understanding skin morphogenesis across developmental, regenerative and evolutionary levels

“…Hair growth cycle is regulated by a number of intra‐follicular signals, but is also highly sensitive to signalling changes in the extra‐follicular skin macro‐environment . In this issue, Biernaskie's group describes how skin wounding and the ensuing signalling changes alter dermal cell dynamics in hair follicles at the wound edge, and two thought‐provoking articles by Paus et al discuss how cycling hair follicles engage in reciprocal signalling with skin‐resident macrophages and dermal adipocytes, as well as the functional implications of these interactions. Two review articles discuss the cellular and signalling mechanisms that allow hair follicles to repair in response to radiation and chemotherapy damage and resume an interrupted hair growth cycle …”