Interleukin-22 suppresses major histocompatibility complex II in mucosal epithelial cells

Area of Science:

• Immunology
• Cell Biology
• Gastroenterology
• Respiratory Medicine

Background:

• Major Histocompatibility Complex (MHC) II is expressed on mucosal epithelial cells and upregulated during inflammation, infection, and in chronic inflammatory diseases.
• The regulation of epithelial cell-specific MHC II during homeostasis remains largely unexplored.
• Interleukin-22 (IL-22) is a cytokine involved in epithelial barrier function and inflammation.

Purpose of the Study:

• To investigate the role of IL-22 in regulating epithelial cell-specific MHC II expression during homeostasis.
• To elucidate the mechanisms by which IL-22 influences MHC II expression in epithelial cells.

Main Methods:

• Utilized animal models lacking the interleukin-22-receptor (IL-22RA1).
• Employed primary human and murine intestinal and respiratory organoids.
• Used murine models of respiratory virus infection and intestinal epithelial cell defects.

Main Results:

• IL-22 directly downregulated interferon-γ-induced MHC II on primary epithelial cells.
• IL-22 modulated the expression of MHC II antigen A α (H2-Aα) and Class II transactivator (Ciita).
• IL-22RA1-knockout animals exhibited significantly higher MHC II expression on mucosal epithelial cells, indicating IL-22's suppressive role.

Conclusions:

• IL-22 plays a novel role in suppressing epithelial cell MHC II expression, partly through regulating endoplasmic reticulum (ER) stress.
• While IL-22-based therapeutics can ameliorate chronic disease pathology, their use might elevate susceptibility to viral infections.
• Understanding IL-22's regulation of MHC II is crucial for balancing immune responses in mucosal tissues.