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il22

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Official Full Name
interleukin 22
Background
Interleukin-22 (IL-22) is protein that in humans is encoded by the IL22 gene. 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 can be also produced by Th17 cells and likely plays a role in the coordinated response of both adaptive and innate immune systems. 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.
Synonyms
IL22; interleukin 22; TIFa; IL-22; ILTIF; IL-TIF; IL-D110; zcyto18; MGC79382; MGC79384; TIFIL-23; IL-10-related T-cell-derived inducible factor; interleukin-22; IL 10 related T cell derived inducible factor; IL 21; IL 22; IL D110; IL TIF; TIFIL 23; cytokine Zcyto18; IL-10-related T-cell-derived-inducible factor; IL-21; IL-24; Ifnphi6

Interleukin-22 (IL-22), a member of the IL-10 family, has been widely studied for its regenerate ability that reverses the injuries caused by a wide range of agents. Studies has found that IL-22 is involved in mucosal barrier defense, tissue repair, epithelial cell survival and proliferation and plays dual roles in many diseases such as autoimmune disease, infection and malignancy.

IL-22 signaling pathway

IL-22 Figure 1. IL-22 signaling pathway. (Lanfranca M P, et al. 2016)

IL-22 has been found to regulate signaling via binding to a heterodimer receptor complex, which consists of IL-22R1 and IL-10R2. Upon binding of IL-22 to the IL-22R1, the heterodimer complex alters conformation and associates to IL-10R2, activating the downstream signaling. The Janus kinases 1 (Jak1) and tyrosine-protein kinase2 (Tyk2) are first activated and trigger various intracellular pathways such as mitogen-activated protein kinase (MAPK), AKT, P38, JNK and extracellular regulated protein kinases 1/2 (ERK1/2) via phosphorylation of the signal transducer and activator of transcription (STAT)1, STAT3 and, STAT5 proteins. Thus, IL-22 can exert its biological functions in preservation of mucosal barriers, protection of the host from microbial parasites in the skin, lung and intestine, prevention of cellular apoptosis and promotion of cell survival and proliferation (Figure 1). However, it has been demonstrated that the soluble high affinity receptor IL-22 binding protein (IL-22 BP) can regulate the IL-22 function negatively.

IL-22 and intestinal diseases

IL-22 Figure 2. Protective effects of IL-22 against tumor formation. (Hernandez P, et al. 2018)

Studies from various experimental models of colonic injury and inflammation have demonstrated the protective effects of IL-22 against tumor formation (Figure 2). These effects have been proved to mediate by specific chemokines, genes related to promotion of cellular mobility and innate defense mechanisms. It has been shown that IL-22 protects intestinal epithelium from damage and induces intestinal stem cell proliferation and survival to repair intestinal injury. Moreover, IL-22 has been found to involve in limiting inflammation to protect intestines during chronic colitis. The IL-22 protective effects also perform in decreasing the unexpected damage from chemotherapeutic agents. Additionally, IL-22 has been found to interrupt the contact between the intestinal bacteria and the epithelium and protect the intestinal barrier from pathogenic microbes via inducing the production of the mucus layer and anti-bacterial proteins. It also has been shown that IL-22 is involved in the expansion of beneficial bacterial communities, which is against the colonization of potential pathogens, through regulating the production and release of certain carbohydrate chains.

IL-22 Figure 3. IL-22 contributes to tumor progression. (Hernandez P, et al. 2018)

In addition to the protective effects, IL-22 has been found to promote tumor progression, typically at later stages of cancer progression (Figure 3). It has been shown that IL-22/IL-22R signaling is utilized by cancer cells to induce its proliferation which contributes to tumor growth. Moreover, a supporting niche, created under the influence of IL-22 signaling, provides the tumor with nutrient and represses the host antitumor immune responses. Studies have been found that the pro-survival and anti-apoptotic effects of IL-22 on tumor cells might be implicated with the activation of STAT3 signaling, which is known as an oncogenic signaling pathway. Additionally, IL-22 also has been found to enhance migration and invasion of tumor cells via increasing the expression of matrix metalloprotease (MMP) and damaging the basal lamina. Several reports also demonstrated that factors like cellular stress responses and reactive nitrogen species induced by IL-22 might be harmful for DNA, promoting tumor or progression.

References:

  1. Hernandez P, et al. A catch‐22: Interleukin‐22 and cancer. European Journal of Immunology, 2018, 48(1).
  2. Shabgah A G, et al. Interleukin-22 in human inflammatory diseases and viral infections. Autoimmunity Reviews, 2017, 16(12).
  3. Parks O B, et al. Interleukin-22 Signaling in the Regulation of Intestinal Health and Disease. Frontiers in Cell & Developmental Biology, 2015, 3(282):52-57.
  4. Lanfranca M P, et al. Biological and Pathological Activities of Interleukin-22. Journal of Molecular Medicine-jmm, 2016, 94(5):523-534.