Epithelial cell-derived CD83 restores immune tolerance in the airway mucosa by inducing regulatory T-cell differentiation

上皮细胞衍生的 CD83 通过诱导调节性 T 细胞分化恢复气道粘膜的免疫耐受性

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作者:Li-Hua Mo, Xiang-Qian Luo, Gui Yang, Jiang-Qi Liu, Li-Teng Yang, Zhi-Qiang Liu, Shuai Wang, Da-Bo Liu, Zhi-Gang Liu, Ping-Chang Yang

Abstract

The mechanism of generation of regulatory T cells (Treg) remains incompletely understood. Recent studies show that CD83 has immune regulatory functions. This study aims to investigate the role of epithelial cell-derived CD83 in the restoration of immune tolerance in the airway mucosa by inducing the Treg differentiation. In this study, CD83 and ovalbumin (OVA)-carrying exosomes were generated from airway epithelial cells. An airway allergy mouse model was developed to test the role of CD83/OVA-carrying exosomes in the suppression of airway allergy by inducing Treg generation. We observed that mouse airway epithelial cells expressed CD83 that could be up-regulated by CD40 ligand. The CD83 deficiency in epithelial cells retarded the Treg generation in the airway mucosa. CD83 up-regulated transforming growth factor-β-inducible early gene 1 expression in CD4+ T cells to promote Foxp3 expression. Exposure of primed CD4+ T cells to CD83/OVA-carrying exosomes promoted antigen-specific Treg generation. Administration of CD83/OVA-carrying exosomes inhibited experimental airway allergic response. In summary, airway epithelial cells express CD83 that is required in the Treg differentiation in the airway mucosa. Administration of CD83/OVA-carrying exosomes can inhibit airway allergy that has the translation potential in the treatment of airway allergic disorders.

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