Interleukin 22 Explained

Interleukin-22 (IL-22) is a protein that in humans is encoded by the IL22 gene.[1]

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.[2]

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 is produced by several populations of immune cells at a site of inflammation. Producers are αβ T-cell classes Th1, Th22 and Th17 along with γδ T cells, NKT, ILC3, neutrophils and macrophages. IL-22 takes effect on non-hematopoietic cells – mainly stromal and epithelial cells. Effects involve stimulation of cell survival, proliferation and synthesis of antimicrobials including S100, Reg3β, Reg3γ and defensins. IL-22 thus participates in both wound healing and in protection against microbes.[3] IL-22 dysregulation takes part in pathogenesis of several autoimmune diseases like systemic lupus erythematosus, rheumatoid arthritis and psoriasis.[4]  

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.[5] 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.[6] In some contexts, the pro-inflammatory versus tissue-protective functions of IL-22 are regulated by the often co-expressed cytokine IL-17A [7]

Target tissue

Targets of this cytokine are mostly non-hematopoietic cells – epithelial and stromal cells of following tissues and organs: liver, lung, skin, thymus, pancreas, kidney, gastrointestinal tract, synovial tissues, heart, breast, eye and adipose tissue.

Signaling

IL-22 is 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),[8] 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.[9]

IL-22, signals through the interferon receptor-related proteins CRF2-4 and IL-22R.[10] 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.

Regulation of production

IL-22 production is induced mainly through IL-23 receptor signalling. IL-23 is produced by dendritic cells after recognition of ligands by specific Toll-like receptors especially in combination with Dectin-1 and or NOD2 signalling. IL-1β stimulates IL-22 production too. On the other hand IL-22 binding protein is a soluble inhibitor which blocks receptor binding site of IL-22.

Further reading

Notes and References

  1. Dumoutier L, Van Roost E, Colau D, Renauld JC . Human interleukin-10-related T cell-derived inducible factor: molecular cloning and functional characterization as an hepatocyte-stimulating factor . Proceedings of the National Academy of Sciences of the United States of America . 97 . 18 . 10144–9 . August 2000 . 10954742 . 27764 . 10.1073/pnas.170291697 . 2000PNAS...9710144D . free .
  2. Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R . IL-22 increases the innate immunity of tissues . Immunity . 21 . 2 . 241–54 . August 2004 . 15308104 . 10.1016/j.immuni.2004.07.007 . free .
  3. Dudakov JA, Hanash AM, van den Brink MR . Interleukin-22: immunobiology and pathology . Annual Review of Immunology . 33 . 1 . 747–85 . 2015-03-21 . 25706098 . 10.1146/annurev-immunol-032414-112123 . 4407497 .
  4. Pan HF, Li XP, Zheng SG, Ye DQ . Emerging role of interleukin-22 in autoimmune diseases . Cytokine & Growth Factor Reviews . 24 . 1 . 51–7 . February 2013 . 22906768 . 10.1016/j.cytogfr.2012.07.002 . 4003867 .
  5. Jones BC, Logsdon NJ, Walter MR . Structure of IL-22 bound to its high-affinity IL-22R1 chain . Structure . 16 . 9 . 1333–44 . September 2008 . 18599299 . 2637415 . 10.1016/j.str.2008.06.005 .
  6. Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A . Interleukin-10 and the interleukin-10 receptor . Annual Review of Immunology . 19 . 683–765 . 2001 . 11244051 . 10.1146/annurev.immunol.19.1.683 . .
  7. Sonnenberg GF, Nair MG, Kirn TJ, Zaph C, Fouser LA, Artis D . Pathological versus protective functions of IL-22 in airway inflammation are regulated by IL-17A . The Journal of Experimental Medicine . 207 . 6 . 1293–305 . June 2010 . 20498020 . 2882840 . 10.1084/jem.20092054 .
  8. Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher PB . Interleukin-10 and related cytokines and receptors . Annual Review of Immunology . 22 . 929–79 . 2004 . 15032600 . 10.1146/annurev.immunol.22.012703.104622 .
  9. Witte K, Witte E, Sabat R, Wolk K . IL-28A, IL-28B, and IL-29: promising cytokines with type I interferon-like properties . Cytokine & Growth Factor Reviews . 21 . 4 . 237–51 . August 2010 . 20655797 . 10.1016/j.cytogfr.2010.04.002 .
  10. Xie MH, Aggarwal S, Ho WH, Foster J, Zhang Z, Stinson J, Wood WI, Goddard AD, Gurney AL . 6 . Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R . The Journal of Biological Chemistry . 275 . 40 . 31335–9 . October 2000 . 10875937 . 10.1074/jbc.M005304200 . free .