Myeloid dendritic cells stimulated by thymic stromal lymphopoietin promote Th2 immune responses and the pathogenesis of oral lichen planus.

Masaki Yamauchi,Masafumi Moriyama,Sachiko Furukawa,Akihiko Tanaka,Takashi Maehara,Noriko Ishiguro,Jun-Nosuke Hayashida,Miho Ohta,Seiji Nakamura,Keigo Kubota,Mizuki Sakamoto,Hiroyasu Nakano

doi:10.1371/journal.pone.0173017

Abstract

Oral lichen planus (OLP) is a chronic inflammatory disease characterized by subepithelial T-cell infiltration. Recent studies reported that specific T helper (Th) subsets, especially Th2 cells, are involved in the pathogenesis of OLP. Thymic stromal lymphopoietin (TSLP) is mainly secreted by epithelial cells and potently activates myeloid dendritic cells (mDCs) to induce Th2-mediated inflammation. Here, we investigated the expression of TSLP and related molecules in OLP. Buccal mucosa specimens from patients with OLP, hyperkeratosis, and ulcer were analyzed by immunohistochemistry for expression of TSLP, its receptor (TSLPR), and inflammatory cells. TSLP was detected in/around the epithelium of patients with OLP and hyperkeratosis, whereas TSLPR, CD11c (mDC), and GATA3 (Th2) were strongly expressed in the subepithelial layer only in OLP patients. Double immunofluorescence staining showed that TSLPR expression mainly co-localized with CD11c. Moreover, the number of CD11c- and GATA-3 positive cells was correlated in OLP patients. In lesions selectively extracted by laser microdissection, the mRNA expression of Th2 (IL-4, MDC, TARC, GATA3)- and Th17 (IL-17, RORγt)-related molecules in OLP patients was significantly higher than in other groups. These results suggest that CD11c+ mDCs expressing TSLPR contribute to aberrant Th2 immune responses and the pathogenesis of OLP via TSLP stimulation.

Highlights

Oral lichen planus (OLP) is a chronic inflammatory disease characterized by abnormally keratinized oral mucosa and band-like T-cell infiltration in the upper lamina propria
buccal mucosa (BM) specimens from patients with OLP, hyperkeratosis or ulcer were examined after immunohistochemical staining to evaluate the distributions of Thymic stromal lymphopoietin (TSLP) and TSLPR
Expression of TSLPR was only detected in the subepithelium of patients with OLP, where it was strongly detected in infiltrating cells (Fig 1B)

Summary

Introduction

Oral lichen planus (OLP) is a chronic inflammatory disease characterized by abnormally keratinized oral mucosa and band-like T-cell infiltration in the upper lamina propria. It is referred to as a potentially malignant disorder by the World Health Organization. MDCs stimulated by TSLP and Th2 activation in OLP working group [1,2,3]. OLP is classified into seven forms: atrophic, bullous, erosive, popular, pigmented, plaquelike; or reticular. The patients with reticular lesions, the most common form, generally have no clinical symptoms, while atrophic, bullous, and erosive lesions cause pain, ranging from mild to severe. Erosive OLP shows a significantly higher rate of malignant transformation than non-erosive OLP [3]

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Conclusion