Interleukin 22

Interleukin 22
250px Crystallographic structure of IL-22 (rainbow colored, N-terminus = blue, C-terminus = red) complexed with the IL-22R1 (magenta).
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1M4R, 1YKB, 3DGC, 3DLQ, 3G9V, 3Q1S
Identifiers
Symbols	IL22 ; IL-21; IL-22; IL-D110; IL-TIF; ILTIF; TIFIL-23; TIFa; zcyto18
External IDs	OMIM: 605330 MGI: 2151139 HomoloGene: 9669 GeneCards: IL22 Gene
Gene ontology Molecular function • cytokine activity • interleukin-22 receptor binding Cellular component • extracellular region • extracellular space Biological process • acute-phase response • inflammatory response • cell-cell signaling • response to glucocorticoid Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	50616	50929
Ensembl	ENSG00000127318	ENSMUSG00000074695
UniProt	Q9GZX6	Q9JJY9
RefSeq (mRNA)	NM_020525	NM_016971
RefSeq (protein)	NP_065386	NP_058667
Location (UCSC)	Chr 12: 68.25 – 68.25 Mb	Chr 10: 118.2 – 118.21 Mb
PubMed search	[1]	[2]

Interleukin-22 (IL-22) is protein that in humans is encoded by the IL22 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 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 T cells and initiates innate immune responses against bacterial pathogens especially in 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 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 signal transduction to selectively initiate and regulate immune responses. IL-22 can contribute to immune disease through the stimulation of inflammatory responses, S100s and defensins. IL-22 also promotes 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 hepatocytes, keratinocytes, and lung and intestinal epithelial cells. 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 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 (JAK1, Tyk2, and MAP kinases) and transcription factors, especially STAT3. It can induce IL-20 and IL-24 signaling when IL-22R1 pairs with IL-20R2.