The two faces of mast cells in vitiligo pathogenesis

Ichiro Katayama,Fei Yang,Aya Takahashi,Lingli Yang,Mari Wataya-Kaneda

doi:10.37349/ei.2021.00018

Ichiro Katayama, Fei Yang + Show 3 more

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https://doi.org/10.37349/ei.2021.00018

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Abstract

Aim: Previously, we reported increased number of T helper 17 (Th17) cells in vitiligo. However, in our recent study, tryptase and interleukin (IL)17 double positive cells which identified by polyclonal anti-IL17 antibody with specificity for IL17A, B, D, F was observed, but these mast cells cannot be stained by monoclonal anti-IL17 antibody with specificity for IL17A. Therefore, this study was aimed to clarify the role of mast cells in induction and progression of vitiligo. Methods: Mast cells were stained with two antibodies against IL17 and one antibody against tryptase by immunofluorescent staining. Furthermore, immunoelectron microscopy (IEM) analyses were conducted using anti-tryptase. In vitro, cultured epidermal keratinocytes were treated with agents which released by mast cells. Expression levels of mRNA were analyzed by real-time polymerase chain reaction (PCR), expression of protein levels was analyzed by western blotting. Results: An increased number of tryptase positive mast cells was observed at the lesional skin of upper dermis in vitiligo and rhododendrol-induced leukoderma (RDIL). These mast cells showed prominent degranulation in vitiligo. Interestingly, the melanosome forming glycoprotein non-metastatic melanoma protein B (GPNMB) is downregulated in the lesional basal keratinocytes in vitiligo and mast cell tryptase contributes to this phenomenon. In addition, small interfering GPNMB RNA (siGPNMB RNA)-introduced keratinocytes increased melanocyte survival through stem cell factor (SCF) production in the melanocyte/keratinocyte co-culture system. Conclusions: Mast cells might be two-faced in vitiligo induction, progression, and recovery through the differential function of histamine and tryptase.

Highlights

Vitiligo vulgaris is common depigmented skin disorder characterized with loss of functional melanocytes
We have previously reported that IL17A-producing T helper 17 (Th17) cells infiltrated to the lesional skin in vitiligo and IL17A stimulated fibroblast- and keratinocyte-generated proinflammatory cytokines, such as tumor necrosis factor α (TNF-α), IL1, or IL6
Mast cells were not identified by the monoclonal anti IL17A (AHP455G; specificity IL17A) antibody (Figure 1B and C), these results suggest that these mast cells might contain the non-A subtype of IL17 and mast cell extracellular trap PAF (MET) [10] might occur in vitiligo, similar to those observed in psoriasis or rheumatoid arthritis and provides one possible explanation for the increase in IL17+ cell infiltration into the lesional skin vitiligo [9]

Summary

Introduction

Vitiligo vulgaris is common depigmented skin disorder characterized with loss of functional melanocytes. It is a multifactorial disorder with a complex pathogenesis. The pathogenesis theories include oxidative stress, neurotoxic effect, CD8+ cytotoxic T cells and autoantibodies against melanocyte. Inflammatory cytokine expression which are reported increased in vitiligo, such as that of interleukin (IL), tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ), or IL2, and reduced endothelin-1 (ET-1) or stem cell factor (SCF) expression exhibit melanocyte-stimulating activity [3, 4]. It is well known that hypermelanosis is observed in the surrounding skin of vitiligo and drug-induced photo-leukoderma, similar clinical features are observed in cosmetic-induced rhododendrol-induced leukoderma (RDIL) from Japan [5,6,7]

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