Signs of atopic dermatitis and contact dermatitis affected by distinct H2-haplotype in the NC/Nga genetic background

Teruyo Tsukada,Yuki Okuno,Kimimasa Takahashi,Daiki Ito,Kozo Ohkusu-Tsukada

doi:10.1038/s41598-018-21049-x

Teruyo Tsukada, Yuki Okuno + Show 3 more

Open Access

https://doi.org/10.1038/s41598-018-21049-x

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Abstract

We recently advocated in favour of naming a novel H2-haplotype consisting of Kd, D/Ldm7, I-Ak and I-Ek in the atopic dermatitis (AD) mouse model NC/Nga as “H-2nc.” The role of the H2-haplotype in AD development was investigated in H2b-congenic NC/Nga mice (NC.h2b/b and NC.h2b/nc) established by backcrossing. A severe 2,4-dinitrofluorobenzene (DNFB)-induced dermatitis in NC/Nga was alleviated partially in NC.h2b/nc and significantly in NC.h2b/b. The AD phenotype was correlated with thymic stromal lymphopoietin (TSLP)-epidermal expression levels and serum levels of total IgE and IL-18/IL-33. Histologically, allergic contact dermatitis (ACD) was accompanied by lymphocytes and plasma cells-infiltrating perivasculitis in NC.h2b/nc and NC.h2b/b and clearly differed from AD accompanied by neutrophils, eosinophils and macrophages-infiltrating diffuse suppurative dermatitis in NC/Nga. Interestingly, IFN-γ/IL-17 production from autoreactive CD4+ T-cells remarkably increased in DNFB-sensitised NC.h2b/b but not in NC/Nga. Our findings suggest that AD or ACD may depend on haplotype H-2nc or H-2b, respectively, in addition to the NC/Nga genetic background.

Highlights

Because Atopic dermatitis (AD)-like disease can develop in DNFB-applied BALB/c mice by adaptive transfer of immunoglobulin E (IgE) recognising DNFB as a hapten[5], the immunoglobulin class switching to IgE is possible key for the development of AD-like disease
Even though IL-4 is a major cytokine for IgE-class switching[6], the mechanism underlying the hyperproduction of IgE is not dependent on IL-4 levels in DNFB-treated NC/Nga mice but could rely on IL-13 inducing IL-4-independent IgE synthesis[7,8]
DNFB-induced dermatitis in NC/Nga, NC.h2b/b and NC.h2b/nc was evaluated by both a scoring index of AD19 and the myeloperoxidase (MPO) activity using in vivo Imaging System

Summary

Introduction

DNFB-induced dermatitis in NC/Nga mice under SPF condition is associated with the development of AD-like disease (type I allergy) rather than ACD-like disease (type IV allergy)[2]. Our group recently found that the clonal deletion of T cell repertoires with specific T cell receptor Vβ chains is induced by the expression of two endogenous superantigens (Mls-1a, MMTV(SHN)) in the genetic background of NC/Nga mice[14] This finding was in line with a previous report showing that under conventional condition, the Th1 dominant state mediated by IL-12 or IL-18 after Staphylococcal enterotoxin B (SEB) exposure was inhibited by the absence of Vβ8+ T-cells in NC/Nga mice, resulting in the induction of the Th2 dominant state[15]. The role of the H2-haplotype in AD development in the NC/Nga strain is discussed

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