Swine IL-22 (Interleukin-22) is a member of the IL-10 cytokine family that plays a key role in mucosal immunity and epithelial barrier protection in pigs (Sus scrofa). IL-22 is produced primarily by activated CD4⁺ T cells, including Th17- and Th22-like subsets, as well as by γδ T cells and innate lymphoid cells (ILC3s), in response to microbial infection and inflammatory stimulation. It signals through the IL-22 receptor complex (IL-22R1 and IL-10R2), expressed mainly on epithelial and stromal cells, activating downstream JAK/STAT pathways—particularly STAT3—to induce antimicrobial peptide production, enhance chemokine expression, promote epithelial cell proliferation, and support tissue repair. In healthy swine, basal IL-22 expression is generally low but increases during bacterial, viral, and parasitic infections, particularly at mucosal surfaces of the gastrointestinal and respiratory tracts. Swine IL-22 has been implicated in immune responses to enteric pathogens such as Escherichia coli and Salmonella, as well as respiratory pathogens including porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus. In veterinary and translational research, swine IL-22 serves as a biomarker of mucosal immune activation and epithelial defense and is studied in the context of host–pathogen interactions, vaccine efficacy, and maintenance of barrier integrity in both agricultural and biomedical disease models.