Costimulatory Molecule CD226 Regulates Atopic Dermatitis in a Mouse Model

Wei Qiao; Chujun Duan; Jingchang Ma; Wei Hu; Yang Xie; Lu Yang; Tingting Wang; Shuwen Wu; Xuemei Li; Yuling Wang; Kun Cheng; Yun Zhang; Yuan Zhang; Ran Zhuang

doi:10.1016/j.jid.2024.01.022

Costimulatory Molecule CD226 Regulates Atopic Dermatitis in a Mouse Model

J Invest Dermatol. 2024 Feb 6:S0022-202X(24)00099-X. doi: 10.1016/j.jid.2024.01.022. Online ahead of print.

Authors

Wei Qiao¹, Chujun Duan¹, Jingchang Ma², Wei Hu², Yang Xie³, Lu Yang², Tingting Wang⁴, Shuwen Wu⁵, Xuemei Li², Yuling Wang², Kun Cheng², Yun Zhang², Yuan Zhang⁶, Ran Zhuang⁷

Affiliations

¹ Institute of Medical Research, Northwestern Polytechnical University, Xi'an, China; Department of Immunology, Fourth Military Medical University, Xi'an, China.
² Department of Immunology, Fourth Military Medical University, Xi'an, China.
³ Otolaryngological Department of Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
⁴ Department of Immunology, Fourth Military Medical University, Xi'an, China; Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
⁵ Institute of Medical Research, Northwestern Polytechnical University, Xi'an, China.
⁶ Department of Immunology, Fourth Military Medical University, Xi'an, China. Electronic address: zhangyuan@fmmu.edu.cn.
⁷ Department of Immunology, Fourth Military Medical University, Xi'an, China. Electronic address: fmmuzhr@fmmu.edu.cn.

PMID: 38325579
DOI: 10.1016/j.jid.2024.01.022

Abstract

This study investigated the role of CD226 in a 2,4-dinitrochlorobenzene (DNCB)-induced mouse model of atopic dermatitis. The results showed that the lack of CD226 (global and CD4⁺ T-cell specific) significantly increased ear thickness, reddening, swelling, and scaling of the skin as well as inflammatory cell and mast cell infiltration. RT-qPCR results demonstrated that the mRNA expressions of atopic dermatitis-related inflammatory cytokines and chemokines were markedly increased in the draining lymph nodes and lesioned ear skin tissues of global and CD4⁺ T-cell-specific CD226-deficient mice compared with that in control mice. In vitro assessment revealed that CD226 directly modulates TGFβ-mediated regulatory T (Treg) cell differentiation and proliferation. Notably, Treg cell-specific deletion of CD226 (Cd226^fl/flFoxp3^cre mice) resulted in more severe dermatitis and epidermal thickening than those observed in littermate mice upon DNCB treatment. Subsequent analysis showed that the infiltration of Treg cells in ear lesions and the number of Tregs in the spleen were significantly reduced in Cd226^fl/flFoxp3^cre mice after DNCB treatment. In addition, the lack of CD226 induced apoptosis of Treg cells through the activation of caspase 3. Therefore, these results suggest that CD226 has potential efficacy in atopic dermatitis, correlating with Treg cell inhibition.

Keywords: CD226; CD4(+) T cell; atopic dermatitis; regulatory T cell.