The human hair follicle immune system: cellular composition and immune privilege

TLDR

The hair follicle’s immune system, its link to skin immunity, and its relevance to hair disorders are biologically intriguing and clinically important. The study aimed to map cellular composition and immune privilege of the human hair follicle during anagen VI using 15 immunodermatological markers. Immunohistochemical and TEM analysis revealed that Langerhans cells, CD4⁺ and CD8⁺ T cells, macrophages, and mast cells populate the distal follicular epithelium and perifollicular connective tissue, with very few immune cells in the proximal epithelium and dermal papilla, and melanophages present in the connective tissue sheath and papilla. Reduced MHC class I/β2‑microglobulin expression, lack of Fas ligand, and diminished Langerhans and T cells in the proximal follicle indicate an immune‑privileged zone whose breakdown may drive alopecia areata.

Abstract

The immunology of the hair follicle, its relationship with the 'skin immune system' and its role in hair diseases remain biologically intriguing and clinically important. In this study, we analysed the immunoreactivity patterns of 15 immunodermatological markers to determine the cellular composition and immune privilege of the human hair follicle immune system in anagen VI (growth phase). The most prominent cells located in or around the hair follicle were Langerhans cells, CD4+ or CD8+ T cells, macrophages and mast cells, whereas B cells, natural killer cells and γδ T cells were found very rarely. Langerhans cells (CD1a+, major histocompatibility complex, MHC class II+), and T cells (CD4+ or CD8+) were predominantly distributed in the distal hair follicle epithelium, whereas macrophages (CD68+, MHC class II+) and mast cells (Giemsa+) were located in the perifollicular connective tissue sheath. Transmission electron microscopy confirmed low numbers of immune cells in the proximal hair follicle epithelium, and very few macrophages and Langerhans cells were seen in the dermal papilla. Melanophages were observed in the connective tissue sheath and dermal papilla. MHC class I (HLA‐A, ‐B, ‐C) and β2‐microglobulin immunoreactivity was found on most skin cells, but was substantially reduced on isthmus keratinocytes and virtually absent in the proximal hair follicle epithelium. Apart from the absence of Fas ligand immunoreactivity, the sharply reduced numbers of T cells and Langerhans cells, and the virtual absence of MHC class I expression all suggest that the anagen proximal hair follicle constitutes an area of immune privilege within the hair follicle immune system, whose collapse may be crucial for the pathogenesis of alopecia areata.