IL-22: Immunity's bittersweet symphony

Abstract

Epithelial cells play a crucial role in barrier defense. Here, Moniruzzaman et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20230106) discovered that interleukin-22 (IL-22) represses MHC class II expression by epithelial cells with an opposite impact on chronic inflammatory disease and viral infection.

Insights from Jinzhi Duan, Juan D. Matute, and Richard S. Blumberg.

Dual role of IL-22 in immune response modulation. IL-22 exhibits a dual function, acting as both an anti-inflammatory cytokine during chronic gut inflammation and a pro-inflammatory cytokine during acute lung infection. The binding of IL-22 to the heterodimeric receptor complex IL-22Rα/IL-10Rβ initiates JAK-STAT signaling. In this pathway, phosphorylated STAT1 and STAT3 may negatively regulate MHC II expression by suppressing ER stress. Activated ER stress can lead to the upregulation of MHC II or Ciita, the critical transcription factor responsible for MHC II expression in ECs. Alternatively, phosphorylated STAT1 and STAT3 might directly inhibit the expression of Ciita, consequently downregulating MHC II expression. The question marks within the figure indicate speculative hypotheses, necessitating further direct experimental validation.