Downregulation of integrin‐αvβ6 on keratinocytes in the scar of lichen planopilaris and folliculitis decalvans: Relevance for the disappearance of epidermal Langerhans cells

Abstract

Primary cicatricial alopecia (PCA) is a group of poorly understood mechanisms in which the destruction of hair follicles leads to permanent hair loss. Lichen planopilaris (LPP) is a type of lymphocytic PCA and it has been known for epidermal Langerhans cells (LC) to disappear in the scar of LPP. We also found that epidermal LC also disappeared in the scar of folliculitis decalvans (FD), a type of neutrophilic PCA. Of note was that epidermal LC did not disappear in the scar of discoid lupus erythematosus, another type of lymphocytic PCA, suggesting that LC disappearance in the scar was not always a common feature of PCA. We found that the expression of integrin (ITG)‐αvβ6 in scar epidermis was significantly diminished in LPP and FD, but not in other PCA and disorders accompanied with scar formation. We also found that exogenous interleukin‐1β and α‐interferon downregulated ITG‐αvβ6 expression in normal human epidermal keratinocytes. These data suggest that downregulation of ITG‐αvβ6 may be one of the causes of LC disappearance in the scar of LPP and FD.

A niche in the spotlight: Could external factors critically disturb hair follicle homeostasis and contribute to inflammatory hair follicle diseases?

“…[ 58 ] Enhanced LC/T lymphocyte ratios were reported in lichen planopilaris compared to traction alopecia, [ 59 ] while a loss of LCs in interfollicular epidermis was described in association with hair follicle destruction in lichen planopilaris and folliculitis decalvans. [ 60 ] Perifollicular and intrafollicular LCs appear to be increased in hair follicle affected the frontal fibrosing alopecia, [ 61 ] but most investigations are limited to immunohistochemical stainings of patient biopsies.…”

Immunohistochemical analysis of S100-positive epidermal Langerhans cells in dermatofibroma

“…The increased density of LCs in the peritumoral epidermis of dermatofibroma suggests strong immunologic response of this area to hinder the growth of the tumor, resulting in a more localized and restricted form of the dermal fibrohistiocytic proliferation. This upregulation of LCs may be due to alterations in the growth factors and cytokines, 7 apoptosis, and the direct cytotoxic effects of the tumor cells. Several proteins are associated with the development, differentiation, and maintenance of LCs, such as transforming growth factor-beta (TGFβ), IL-34, BMP-7, integrin (ITG) avb6, and ITGavb8.…”

“…Several proteins are associated with the development, differentiation, and maintenance of LCs, such as transforming growth factor-beta (TGFβ), IL-34, BMP-7, integrin (ITG) avb6, and ITGavb8. 7 , 8 This author proposes that the increased density of LCs in the peritumoral epidermis of dermatofibroma is due to upregulation of these molecules. Activins A (TGFβ family members) can induce the differentiation of human monocytes into LCs and therefore are important for populating the epidermis with LCs.…”

“…It is worthwhile to examine the alterations of the molecules contributing to quantitative deficit of LCs in the epidermis overlying dermatofibroma, such as TGFβ, IL-34, BMP-7, ITGavb6, and ITGavb8. 7 , 8 …”