Interleukin 22

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Interleukin 22
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Crystallographic structure of IL-22 (rainbow colored, N-terminus = blue, C-terminus = red) complexed with the IL-22R1 (magenta).[1]
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols IL22 ; IL-21; IL-22; IL-D110; IL-TIF; ILTIF; TIFIL-23; TIFa; zcyto18
External IDs OMIM605330 MGI2151139 HomoloGene9669 GeneCards: IL22 Gene
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.[2][3]

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.[4] IL-22R is expressed on tissue cells, and it is absent on immune cells.[5]

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.[4]

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),[6] 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.[7] 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 [8] 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.[9]

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.[4] 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.[10] In some contexts, the pro-inflammatory versus tissue-protective functions of IL-22 are regulated by the often co-expressed cytokine IL-17A [11]

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.[12]

Signaling

IL-22, signals through the interferon receptor-related proteins CRF2-4 and IL-22R.[3] 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.

References

  1. PDB: 3DGC​; Lua error in package.lua at line 80: module 'strict' not found.
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Further reading

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