Suprabasin-null mice retain skin barrier function and show high contact hypersensitivity to nickel upon oral nickel loading

Shinsuke Nakazawa,Sanki Asakawa,Pawit Phadungsaksawasdi,Noriyasu Hirasawa,Takatoshi Shimauchi,Masahiro Aoshima,Jun-Ichi Sakabe,Atsuko Funakoshi,Yoshiki Tokura,Taisuke Ito

doi:10.1038/s41598-020-71536-3

Shinsuke Nakazawa, Sanki Asakawa + Show 8 more

Open Access

https://doi.org/10.1038/s41598-020-71536-3

Copy DOI

Abstract

Suprabasin (SBSN) is expressed not only in epidermis but also in epithelial cells of the upper digestive tract where metals such as nickel are absorbed. We have recently shown that SBSN level is decreased in the stratum corneum and serum of atopic dermatitis (AD) patients, especially in intrinsic AD, which is characterized by metal allergy. By using SBSN-null (Sbsn–/–) mice, this study was conducted to investigate the outcome of SBSN deficiency in relation to AD. Sbsn–/– mice exhibited skin barrier dysfunction on embryonic day 16.5, but after birth, their barrier function was not perturbed despite the presence of ultrastructural changes in stratum corneum and keratohyalin granules. Sbsn–/– mice showed a comparable ovalbumin-specific skin immune response to wild type (WT) mice and rather lower contact hypersensitivity (CHS) responses to haptens than did WT mice. The blood nickel level after oral feeding of nickel was significantly higher in Sbsn–/– mice than in WT mice, and CHS to nickel was elevated in Sbsn–/– mice under nickel-loading condition. Our study suggests that the completely SBSN deficient mice retain normal barrier function, but harbor abnormal upper digestive tract epithelium that promotes nickel absorption and high CHS to nickel, sharing the features of intrinsic AD.

Highlights

Suprabasin (SBSN) is expressed in epidermis and in epithelial cells of the upper digestive tract where metals such as nickel are absorbed
It is well known that extrinsic atopic dermatitis (AD) is caused by an impaired barrier function of the stratum corneum[6,8], which is represented by the loss-of-function mutation of filaggrin (FLG)[9,10]
We have recently reported that amounts of SBSN in both stratum corneum[16] and serum s amples[17] from AD patients are decreased compared to normal subjects

Summary

Introduction

Suprabasin (SBSN) is expressed in epidermis and in epithelial cells of the upper digestive tract where metals such as nickel are absorbed. We have recently shown that SBSN level is decreased in the stratum corneum and serum of atopic dermatitis (AD) patients, especially in intrinsic AD, which is characterized by metal allergy. Our study suggests that the completely SBSN deficient mice retain normal barrier function, but harbor abnormal upper digestive tract epithelium that promotes nickel absorption and high CHS to nickel, sharing the features of intrinsic AD. The causes and mechanisms of intrinsic AD remain unclear This subtype is immunologically characterized by high frequencies of circulating Th1 and Th17 cells in the peripheral b lood[12] and positive correlations between lesional skin Th17-related molecules and AD severity s cores[13]. In SBSN-deficient 3-dimensional-reconstructed epidermis, there was abnormal epidermal differentiation, including compact stratum corneum and immature keratohyalin granules, independent of other differentiation markers, such as involucrin (IVL), claudin-1, and calpain-117

Methods

Results

Conclusion