IL22 is a cytokine that modulates tissue responses during inflammation and plays an essential role in epithelial cell regeneration to maintain barrier function after injury. Unlike most cytokines, it acts exclusively on non-immune cells, signaling through a heterodimeric receptor composed of IL22RA1 and IL10RB that activates JAK1, TYK2, and subsequently STAT3, promoting cell survival and proliferation through STAT3, ERK1/2, and PI3K/AKT pathways. In the intestine, IL-22 is produced by group 3 innate lymphoid cells and CD4+ T cells 12. It is required for Paneth cell formation and upregulates antimicrobial peptide expression across multiple epithelial cell types, supporting intestinal immunity 3. During intestinal infection, IL-22 maintains epithelial barrier integrity and fluid-ion absorption; loss of IL-22 leads to enterocyte depletion and dehydration rather than failure of antimicrobial or regenerative responses 4. In inflammatory bowel disease, IL-22 production by ILC3s is enhanced through the IRE1α/XBP1 pathway 5, and neutrophils are essential for γδ T cell polarization and IL-22 production 6. IL-22 also contributes to skin barrier dysfunction in atopic dermatitis 78. The monoclonal antibody fezakinumab blocks IL-22 signaling in clinical development for inflammatory diseases.