Genomes and Genes
Gene Symbol: IL 22
Description: interleukin 22
Alias: IL-21, IL-22, IL-D110, IL-TIF, ILTIF, TIFIL-23, TIFa, zcyto18, interleukin-22, IL-10-related T-cell-derived inducible factor, cytokine Zcyto18
Products: IL 22
- Yu L, Wang H, Yang S, Yuan Z, Xu F, Sun C, et al. Expression of interleukin-22/STAT3 signaling pathway in ulcerative colitis and related carcinogenesis. World J Gastroenterol. 2013;19:2638-49 pubmed publisher..IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC. ..
- Ding G, Zhang G, Chen X, ZHANG M, Yang L, Wang Z. [A study on the relationship between single nucleotide polymorphisms of interleukin-22 and susceptibility to pulmonary tuberculosis]. Zhonghua Jie He He Hu Xi Za Zhi. 2012;35:596-600 pubmed..The allele G was the risk factor of pulmonary tuberculosis. The SNP (rs2227473) may play an important role in the protective immune process against tuberculosis by affecting the IL-22 expression of PBMCs. ..
- Ciccia F, Guggino G, Rizzo A, Ferrante A, Raimondo S, Giardina A, et al. Potential involvement of IL-22 and IL-22-producing cells in the inflamed salivary glands of patients with Sjogren's syndrome. Ann Rheum Dis. 2012;71:295-301 pubmed publisher..Th17 and NKp44(+) NK cells were the major cellular sources of IL-22 in patients with pSS. Our results suggest that, together with IL-17 and IL-23, IL-22 may play a pro-inflammatory role in the pathogenesis of pSS. ..
- Jiang R, Wang H, Deng L, Hou J, Shi R, Yao M, et al. IL-22 is related to development of human colon cancer by activation of STAT3. BMC Cancer. 2013;13:59 pubmed publisher..In this study we demonstrated that excessive IL-22 in the CC and UC microenvironment leads to tumor growth, inhibition of apoptosis, and promotion of metastasis depend on STAT3 activation. ..
- Dhiman R, Indramohan M, Barnes P, Nayak R, Paidipally P, Rao L, et al. IL-22 produced by human NK cells inhibits growth of Mycobacterium tuberculosis by enhancing phagolysosomal fusion. J Immunol. 2009;183:6639-45 pubmed publisher..tuberculosis through production of IL-22, which inhibits intracellular mycobacterial growth by enhancing phagolysosomal fusion. IL-15 and DAP-10 elicit IL-22 production by NK cells in response to M. tuberculosis. ..
- Thompson C, Plummer S, Tucker T, Casey G, Li L. Interleukin-22 genetic polymorphisms and risk of colon cancer. Cancer Causes Control. 2010;21:1165-70 pubmed publisher..52, 95% CI = 1.12-2.06, p = 0.0073). Our findings suggest that the rs1179251 SNP in IL-22 is associated with risk of colon cancer. ..
- Wen Z, Liao Q, Zhao J, Hu Y, You L, Lu Z, et al. High expression of interleukin-22 and its receptor predicts poor prognosis in pancreatic ductal adenocarcinoma. Ann Surg Oncol. 2014;21:125-32 pubmed publisher..These findings reveal the positive role of IL-22 and IL-22R in invasion and metastasis in human PDAC. IL-22 and IL-22R may be suitable independent prognostic markers in PDAC. ..
- Kobold S, Völk S, Clauditz T, Küpper N, Minner S, Tufman A, et al. Interleukin-22 is frequently expressed in small- and large-cell lung cancer and promotes growth in chemotherapy-resistant cancer cells. J Thorac Oncol. 2013;8:1032-42 pubmed publisher..Enhanced IL-22-R1 expression and signaling in chemotherapy-refractory cell lines are indicative of a protumorigenic function of IL-22 and may contribute to a more aggressive phenotype. ..
- Dumoutier L, Van Roost E, Colau D, Renauld J. Human interleukin-10-related T cell-derived inducible factor: molecular cloning and functional characterization as an hepatocyte-stimulating factor. Proc Natl Acad Sci U S A. 2000;97:10144-9 pubmed
- Wong C, Lun S, Ko F, Wong P, Hu S, Chan I, et al. Activation of peripheral Th17 lymphocytes in patients with asthma. Immunol Invest. 2009;38:652-64 pubmed..Pro-inflammatory cytokine IL-23 can exacerbate disease severity by activating pathogenic Th17 lymphocytes to release downstream inflammatory cytokine IL-22 in asthma. ..
- Cai T, Wang Q, Zhou Q, Wang C, Hou S, Qi J, et al. Increased expression of IL-22 is associated with disease activity in Behcet's disease. PLoS ONE. 2013;8:e59009 pubmed publisher..IL-22 was associated with disease activity in BD and correlated with the presence of small vessel inflammation, suggesting that it may be involved in its pathogenesis. ..
- Bard J, Gelebart P, Anand M, Amin H, Lai R. Aberrant expression of IL-22 receptor 1 and autocrine IL-22 stimulation contribute to tumorigenicity in ALK+ anaplastic large cell lymphoma. Leukemia. 2008;22:1595-603 pubmed publisher..To conclude, for the first time, we demonstrate the importance of the IL-22 autocrine pathway in a lymphoid malignancy, and reveal yet another novel function of NPM-ALK. ..
- Aujla S, Chan Y, Zheng M, Fei M, Askew D, Pociask D, et al. IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat Med. 2008;14:275-81 pubmed publisher..These data support the concept that the T(H)17 cell lineage and its effector molecules have evolved to effect host defense against extracellular pathogens at mucosal sites. ..
- Eyerich S, Wagener J, Wenzel V, Scarponi C, Pennino D, Albanesi C, et al. IL-22 and TNF-? represent a key cytokine combination for epidermal integrity during infection with Candida albicans. Eur J Immunol. 2011;41:1894-901 pubmed publisher..In summary, we demonstrate that IL-22 and TNF-? represent a potent, synergistic cytokine combination for cutaneous immunity. ..
- Dambacher J, Beigel F, Zitzmann K, Heeg M, Goke B, Diepolder H, et al. The role of interleukin-22 in hepatitis C virus infection. Cytokine. 2008;41:209-16 pubmed publisher..Taken together, hepatic IL-22 expression is up-regulated in viral hepatitis but IL-22 does not directly regulate antiviral proteins and has, in contrast to IFN-alpha, no effect on HCV replication. ..
- Savan R, McFarland A, Reynolds D, Feigenbaum L, Ramakrishnan K, Karwan M, et al. A novel role for IL-22R1 as a driver of inflammation. Blood. 2011;117:575-84 pubmed publisher..This study documents a previously unknown role of IL-22R1 in inflammation and identifies the involvement of IL-22R1/IL-22 in ALK(+)ALCL. ..
- Dumoutier L, Louahed J, Renauld J. Cloning and characterization of IL-10-related T cell-derived inducible factor (IL-TIF), a novel cytokine structurally related to IL-10 and inducible by IL-9. J Immunol. 2000;164:1814-9 pubmed..Further studies will have to address the possibility that some of the IL-9 activities may be mediated by IL-TIF. ..
- Rutz S, Eidenschenk C, Ouyang W. IL-22, not simply a Th17 cytokine. Immunol Rev. 2013;252:116-32 pubmed publisher..Here, we discuss the production of IL-22 from various T-cell populations as well as protective versus pathogenic roles of IL-22. Finally, we focus on recent advances in our understanding of the molecular regulation of IL-22 in T cells. ..
- Sestito R, Madonna S, Scarponi C, Cianfarani F, Failla C, Cavani A, et al. STAT3-dependent effects of IL-22 in human keratinocytes are counterregulated by sirtuin 1 through a direct inhibition of STAT3 acetylation. FASEB J. 2011;25:916-27 pubmed publisher..In skin affected by psoriasis, SIRT1 is down-regulated by IFN-?, which thus renders psoriatic keratinocytes more prone to respond to IL-22. ..
- Shen H, Goodall J, Hill Gaston J. Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis Rheum. 2009;60:1647-56 pubmed publisher..These data support the hypothesis that Th17 cells, particularly when present in excess of IL-10-producing cells, are involved in the pathogenesis of inflammatory arthritis. ..
- Xiang X, Gui H, King N, Cole L, Wang H, Xie Q, et al. IL-22 and non-ELR-CXC chemokine expression in chronic hepatitis B virus-infected liver. Immunol Cell Biol. 2012;90:611-9 pubmed publisher..We speculate that IL-22 and non-ELR-CXC chemokines synergistically may provide protection in liver inflammation/fibrosis during CHB infection. ..
- Park O, Wang H, Weng H, Feigenbaum L, Li H, Yin S, et al. In vivo consequences of liver-specific interleukin-22 expression in mice: Implications for human liver disease progression. Hepatology. 2011;54:252-61 pubmed publisher..These findings indicate that localized production of IL-22 in the liver promotes hepatocyte survival and proliferation but primes the liver to be more susceptible to tumor development without significantly affecting liver inflammation. ..
- Kotenko S, Izotova L, Mirochnitchenko O, Esterova E, Dickensheets H, Donnelly R, et al. Identification of the functional interleukin-22 (IL-22) receptor complex: the IL-10R2 chain (IL-10Rbeta ) is a common chain of both the IL-10 and IL-22 (IL-10-related T cell-derived inducible factor, IL-TIF) receptor complexes. J Biol Chem. 2001;276:2725-32 pubmed
- Zhu J, Cao Y, Li K, Wang Z, Zuo P, Xiong W, et al. Increased expression of aryl hydrocarbon receptor and interleukin 22 in patients with allergic asthma. Asian Pac J Allergy Immunol. 2011;29:266-72 pubmed..Our results suggested that both AhR and IL-22 might be involved in the pathogenesis of allergic asthma in human and the level of IL-22 might have some relationship with the severity of the disease. ..
- Pennino D, Bhavsar P, Effner R, Avitabile S, Venn P, Quaranta M, et al. IL-22 suppresses IFN-?-mediated lung inflammation in asthmatic patients. J Allergy Clin Immunol. 2013;131:562-70 pubmed publisher..IL-22 controls tissue homeostasis by both proinflammatory and anti-inflammatory effects. However, the anti-inflammatory mechanisms of IL-22 remain poorly investigated...
- Zhang N, Pan H, Ye D. Th22 in inflammatory and autoimmune disease: prospects for therapeutic intervention. Mol Cell Biochem. 2011;353:41-6 pubmed publisher..In summary, Th22 cell plays an important and complicated role in inflammatory and autoimmune disease. ..
- Eyerich K, Foerster S, Rombold S, Seidl H, Behrendt H, Hofmann H, et al. Patients with chronic mucocutaneous candidiasis exhibit reduced production of Th17-associated cytokines IL-17 and IL-22. J Invest Dermatol. 2008;128:2640-5 pubmed publisher..The inability to clear C. albicans in CMC patients could be due to a defect in the immune response of IL-17-producing T cells...
- Leipe J, Schramm M, Grunke M, Baeuerle M, Dechant C, Nigg A, et al. Interleukin 22 serum levels are associated with radiographic progression in rheumatoid arthritis. Ann Rheum Dis. 2011;70:1453-7 pubmed publisherTo study the role of interleukin 22 (IL-22) in rheumatoid arthritis (RA). IL-22 serum levels were measured in patients with early, treatment-naive RA (n=49) and in 45 age- and sex-matched healthy individuals as controls...
- Jiang R, Tan Z, Deng L, Chen Y, Xia Y, Gao Y, et al. Interleukin-22 promotes human hepatocellular carcinoma by activation of STAT3. Hepatology. 2011;54:900-9 pubmed publisher..Excessive IL-22 can be found in the HCC microenvironment, leading to tumor growth, inhibition of apoptosis, and promotion of metastasis due to STAT3 activation. ..
- Brand S, Dambacher J, Beigel F, Zitzmann K, Heeg M, Weiss T, et al. IL-22-mediated liver cell regeneration is abrogated by SOCS-1/3 overexpression in vitro. Am J Physiol Gastrointest Liver Physiol. 2007;292:G1019-28 pubmed..In conclusion, IL-22 promotes liver cell regeneration by increasing hepatic cell proliferation and hepatocyte migration through the activation of Akt and STAT signaling, which is abrogated by SOCS-1/3 overexpression. ..
- Brand S, Beigel F, Olszak T, Zitzmann K, Eichhorst S, Otte J, et al. IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and intestinal epithelial cell migration. Am J Physiol Gastrointest Liver Physiol. 2006;290:G827-38 pubmed..IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and IEC migration. ..
- Mathian A, Parizot C, Dorgham K, Trad S, Arnaud L, Larsen M, et al. Activated and resting regulatory T cell exhaustion concurs with high levels of interleukin-22 expression in systemic sclerosis lesions. Ann Rheum Dis. 2012;71:1227-34 pubmed publisher..Active and diffuse forms of the disease are associated with a FoxP3 signature. Altogether, our data depict a status of regulatory/pro-inflammatory T cell imbalance in SSc. ..
- Kagami S, Rizzo H, Lee J, Koguchi Y, Blauvelt A. Circulating Th17, Th22, and Th1 cells are increased in psoriasis. J Invest Dermatol. 2010;130:1373-83 pubmed publisher..In summary, elevated numbers of circulating inflammatory T cells may contribute to cutaneous inflammation and systemic inflammatory disease that occurs in individuals with psoriasis. ..
- Radaeva S, Sun R, Pan H, Hong F, Gao B. Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation. Hepatology. 2004;39:1332-42 pubmed
- Zhang Y, Cobleigh M, Lian J, Huang C, Booth C, Bai X, et al. A proinflammatory role for interleukin-22 in the immune response to hepatitis B virus. Gastroenterology. 2011;141:1897-906 pubmed publisher..These findings might be relevant to the development of cytokine-based therapies for patients with HBV infection. ..
- Wolk K, Warszawska K, Hoeflich C, Witte E, Schneider Burrus S, Witte K, et al. Deficiency of IL-22 contributes to a chronic inflammatory disease: pathogenetic mechanisms in acne inversa. J Immunol. 2011;186:1228-39 pubmed publisher..We conclude that IL-22 deficiency may contribute to the pathogenesis of certain chronic disorders as postulated in this paper for AI. ..
- Hoegl S, Bachmann M, Scheiermann P, Goren I, Hofstetter C, Pfeilschifter J, et al. Protective properties of inhaled IL-22 in a model of ventilator-induced lung injury. Am J Respir Cell Mol Biol. 2011;44:369-76 pubmed publisher..These data support the hypothesis that IL-22, likely via activation of STAT3 and downstream genes (e.g., SOCS3), is able to protect against cell stretch and pulmonary baro-/biotrauma by enhancing epithelial cell resistibility. ..
- Kryczek I, Lin Y, Nagarsheth N, Peng D, Zhao L, Zhao E, et al. IL-22(+)CD4(+) T cells promote colorectal cancer stemness via STAT3 transcription factor activation and induction of the methyltransferase DOT1L. Immunity. 2014;40:772-784 pubmed publisher..Thus, IL-22(+) cells promote colon cancer stemness via regulation of stemness genes that negatively affects patient outcome. Efforts to target this network might be a strategy in treating colorectal cancer patients. ..
- Xie M, Aggarwal S, Ho W, Foster J, Zhang Z, Stinson J, et al. Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R. J Biol Chem. 2000;275:31335-9 pubmed
- Matthews K, Wilkinson K, Kalsdorf B, Roberts T, Diacon A, Walzl G, et al. Predominance of interleukin-22 over interleukin-17 at the site of disease in human tuberculosis. Tuberculosis (Edinb). 2011;91:587-93 pubmed publisher..We propose that our findings support a role for IL-22 in TB-induced pathology or the resulting repair process. ..
- Hennig B, Frodsham A, Hellier S, Knapp S, Yee L, Wright M, et al. Influence of IL-10RA and IL-22 polymorphisms on outcome of hepatitis C virus infection. Liver Int. 2007;27:1134-43 pubmed..We furthermore report on allele and haplotype frequencies and linkage disequilibrium for IL-10RA and IL-22. Our results indicate that genetic variation in these genes may play a modulatory role in the outcome of hepatitis C infection. ..
- Andoh A, Zhang Z, Inatomi O, Fujino S, Deguchi Y, Araki Y, et al. Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts. Gastroenterology. 2005;129:969-84 pubmed..IL-22 derived from activated T cells acts on SEMFs to elicit expression of proinflammatory cytokines and matrix-degrading molecules indicating proinflammatory/remodeling roles in IBD. ..
- Wang B, Zhao X, Fan Y, Zhang J, Zhao J, Wang K. IL-17A but not IL-22 suppresses the replication of hepatitis B virus mediated by over-expression of MxA and OAS mRNA in the HepG2.2.15 cell line. Antiviral Res. 2013;97:285-92 pubmed publisher..We demonstrated that IL-17A effectively suppressed HBV replication in a noncytopathic manner and the over-expression of MxA and OAS mRNA was involved in the suppression of HBV replication by IL-17A...
- Qin W, Chen L, Pan H, Leng R, Zhai Z, Wang C, et al. Expressions of IL-22 in circulating CD4+/CD8+ T cells and their correlation with disease activity in SLE patients. Clin Exp Med. 2011;11:245-50 pubmed publisher..01). In conclusion, increased frequencies of IL-22-positive CD4+ T cells in patients with SLE and positive correlation with SLEDAI score and lupus nephritis suggest that this cytokine may be implicated in the pathogenesis of the disease. ..
- Zhao J, Zhang Z, Luan Y, Zou Z, Sun Y, Li Y, et al. Pathological functions of interleukin-22 in chronic liver inflammation and fibrosis with hepatitis B virus infection by promoting T helper 17 cell recruitment. Hepatology. 2014;59:1331-42 pubmed publisher..IL-22 plays a pathological role in exacerbating chronic liver inflammation and fibrosis by recruiting hepatic Th17 cells in HBV-infected patients and HBV Tg mice. ..
- Lejeune D, Dumoutier L, Constantinescu S, Kruijer W, Schuringa J, Renauld J. Interleukin-22 (IL-22) activates the JAK/STAT, ERK, JNK, and p38 MAP kinase pathways in a rat hepatoma cell line. Pathways that are shared with and distinct from IL-10. J Biol Chem. 2002;277:33676-82 pubmed..Finally, by overexpressing a STAT3 S727A mutant, we showed that serine phosphorylation is required to achieve maximum transactivation of a STAT responsive promoter upon IL-22 stimulation. ..
- Fukui H, Zhang X, Sun C, Hara K, Kikuchi S, Yamasaki T, et al. IL-22 produced by cancer-associated fibroblasts promotes gastric cancer cell invasion via STAT3 and ERK signaling. Br J Cancer. 2014;111:763-71 pubmed publisher..The invasive ability of gastric cancer cells was significantly enhanced by co-culture with IL-22-expressing CAFs. Interleukin-22 produced by CAFs promotes gastric cancer cell invasion via STAT3 and ERK signalling. ..
- Eun Y, Shin I, Lee Y, Shin S, Kim S, Chung J, et al. Interleukin 22 polymorphisms and papillary thyroid cancer. J Endocrinol Invest. 2013;36:584-7 pubmed publisherIL22RA1 (Interleukin 22 receptor-alpha 1), a member of the class II cytokine receptor family, mediates diverse biologic activities and appears to be important in pathogen defense, wound healing, and tissue reorganization...
- Kim S, Hur M, Choi B, Kim M, Lee Y, Choe Y, et al. A preliminary study of new single polymorphisms in the T helper type 17 pathway for psoriasis in the Korean population. Clin Exp Immunol. 2017;187:251-258 pubmed publisher..In conclusion, we report two new psoriasis-susceptibility loci, in IL17F and JAK2, as well as a newly identified late-onset associated protective JAK2 locus and a protective JAK1 haplotype in the Korean population. ..
- Wu L, Liu S, Liu Y, Guo C, Li H, Li W, et al. Up-regulation of interleukin-22 mediates liver fibrosis via activating hepatic stellate cells in patients with hepatitis C. Clin Immunol. 2015;158:77-87 pubmed publisher..Collectively, our data provide evidence that IL-22 may contribute to the fibrogenesis of HCV-associated liver fibrosis by activating HSCs. ..