Several cell types, in particular epithelial cells, express the receptor for the cytokine IL-22 and upon its recognition produce molecules that are active both locally and systemically. Many different types of lymphocyte secrete IL-22. T(h)17 cells produce IL-22 although the optimal conditions for secretion of IL-17 or IL-22 by T(h)17 cells differ, as do the transcription factors involved. Aryl hydrocarbon receptor is required for IL-22 production by T(h)17, T(h)22 and γδ T cells. T(h)22 cells produce IL-22 in response to IL-6 and tumor necrosis factor α (TNF-α), particularly in the skin, whereas γδ T cells produce IL-22 in response to IL-23, particularly in the lung. NK cells produce IL-22 in response to IL-12 and IL-18 or IL-23. Retinoic acid-related orphan receptorγt-positive innate lymphoid cells, including lymphoid tissue inducer (LTi) and LTi-like cells express IL-22 with IL-23 again enhancing expression. IL-22 is known to be expressed in many chronic inflammatory conditions, including psoriasis and rheumatoid arthritis, and its up-regulation often correlates with disease activity. IL-22 is known to be protective in the gastrointestinal tract in inflammatory bowel disease but may mediate either harmful or helpful inflammatory responses in different models of intestinal infection. Finally, IL-22 may also play an important role in tissue repair.