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

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

来源：Immunology, 2021, 163(3): 310-322.

DOI：10.1111/imm.13317

• airway mucosa
• CD83
• epithelial cell
• immune tolerance
• mucosal immunology

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-beta-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.

• 单位
  南方医科大学