Interleukin 22

Interleukin-22 (IL-22) is is_associated_with::protein that in humans is encoded by the IL22 is_associated_with::gene.

Structure
IL-22 is an α-helical cytokine. IL-22 binds to a heterodimeric cell surface receptor composed of IL-10R2 and IL-22R1 subunits. IL-22R is expressed on tissue cells, and it is absent on immune cells.

Crystallization is possible if the N-linked glycosylation sites are removed in mutants of IL-22 bound with high-affinity cell-surface receptor sIL-22R1. The crystallographic asymmetric unit contained two IL-22-sIL-22R1 complexes.

Function
IL-22 a member of a group of is_associated_with::cytokines called the IL-10 family or IL-10 superfamily (including IL-19, IL-20, IL-24, and IL-26), a class of potent mediators of cellular inflammatory responses. It shares use of IL-10R2 in cell signaling with other members of this family, IL-10, IL-26, IL-28A/B and IL-29. IL-22 is produced by activated DC and is_associated_with::T cells and initiates innate immune responses against bacterial pathogens especially in is_associated_with::epithelial cells such as respiratory and gut epithelial cells. IL-22 along with IL-17 is rapidly produced by splenic LTi-like cells and also produced by is_associated_with::Th17 cells and likely plays a role in the coordinated response of both adaptive innate immune systems, autoimmunity and tissue regeneration.

IL-22 biological activity is initiated by binding to a cell-surface complex composed of IL-22R1 and IL-10R2 receptor chains and further regulated by interactions with a soluble binding protein, IL-22BP, which shares sequence similarity with an extracellular region of IL-22R1 (sIL-22R1). IL-22 and IL-10 receptor chains play a role in cellular targeting and is_associated_with::signal transduction to selectively initiate and regulate immune responses. IL-22 can contribute to immune disease through the stimulation of inflammatory responses, S100s and is_associated_with::defensins. IL-22 also promotes is_associated_with::hepatocyte survival in the liver and epithelial cells in the lung and gut similar to IL-10. In some contexts, the pro-inflammatory versus tissue-protective functions of IL-22 are regulated by the often co-expressed cytokine IL-17A

Target tissue
Targets of this cytokine are mostly non-hematopoietic cells such as is_associated_with::hepatocytes, is_associated_with::keratinocytes, and is_associated_with::lung and is_associated_with::intestinal is_associated_with::epithelial cells. is_associated_with::Pancreatic islets also express high levels of IL-22 receptor. It has been shown to induce islet beta cell regeneration.

Signaling
IL-22, signals through the is_associated_with::interferon receptor-related proteins CRF2-4 and IL-22R. It forms cell surface complexes with IL-22R1 and IL-10R2 chains resulting in signal transduction through receptor, IL-10R2. The IL-22/IL-22R1/IL-10R2 complex activates intracellular kinases (is_associated_with::JAK1, Tyk2, and is_associated_with::MAP kinases) and transcription factors, especially is_associated_with::STAT3. It can induce IL-20 and IL-24 signaling when IL-22R1 pairs with IL-20R2.