| Written | 2010-05 | Pascal Gelebart, Raymond Lai |
| Department of Laboratory Medicine, Pathology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada |
| Identity |
| Alias_symbol (synonym) | ILTIF |
| IL-21 | |
| zcyto18 | |
| IL-TIF | |
| IL-D110 | |
| TIFa | |
| TIFIL-23 | |
| IL-22 | |
| MGC79382 | |
| MGC79384 | |
| Other alias | IL21 |
| HGNC (Hugo) | IL22 |
| LocusID (NCBI) | 50616 |
| Atlas_Id | 44519 |
| Location | 12q15 [Link to chromosome band 12q15] |
| Location_base_pair | Starts at 68248245 and ends at 68253501 bp from pter ( according to hg19-Feb_2009) [Mapping IL22.png] |
| Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
| VOPP1 (7p11.2) / IL22 (12q15) |
| DNA/RNA |
 | |
| Representation of the IL22 gene organization. Interleukin 22 gene and RNA structure. | |
| Description | The gene spans a region of 5.2 kb and the coding part is divided into five exons. |
| Transcription | Only one type of transcript has been described. The 540-nucleotide transcript encodes a protein of 179 amino acid residues. The first and last exons are partially untranslated. |
| Pseudogene | None described so far. |
| Protein |
 | |
| Crystal structure of IL-22 at 2.6 A resolution. Adapted from PDB (access number: 1YKB). | |
| Description | IL-22 is a cytokine composed of 179 residues. |
| Expression | Interleukin 22 (IL-22) is a cytokine that was originally labeled IL-10-related T-cell-derived inducible factor. IL-22 belongs to a family of IL-10-related proteins that includes IL-19, IL-20, IL-24/MDA-7, IL-26/AK155, IL-28 and IL-29. IL-22 production is inducible by IL-9 in T-lymphocytes and is known to exert its function by binding to a heterodimeric receptor complex composed of IL-22R1 and IL-10R2. However, more recently, it has been shown that IL-22 can bind the homodimeric receptor composed of the IL-22RA1 chain. IL-22 is normally produced by natural killer cells and Th-17 T cells, a functional distinct population of human helper T cells recently identified as an important source of IL-22. |
| Localisation | IL-22 is a secreted protein. |
| Function | IL-22 exerts its biological effects through the IL-22 receptor/signaling complex, which expression is largely restricted to epithelial cells. Activation of this complex leads to the activation of various cellular signaling pathways, with the JAK/STAT and MAPK pathways being the best characterized. IL-22, as a Th1 cytokine, has been shown to play important roles in mediating inflammation and the wound healing process. |
| Mutations |
| Note | No mutation has been reported thus far. |
| Implicated in |
| Note | |
| Entity | ALK-positive anaplastic large cell lymphoma (ALK+ALCL) |
| Disease | Anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL), or ALK+ALCL, is a specific type of non-Hodgkin lymphoma characterized by the T/null-cell immunophenotype, consistent expression of CD30 and reciprocal chromosomal translocations involving the ALK gene. In most cases, the chromosomal translocation is that of the t(2;5)(p23;q35) type, which leads to the juxtaposition of the nucleophosmin (NPM) gene at 5q35 to the ALK gene at 2p23. Mounting evidence suggests that the resulting oncogenic fusion protein, NPM-ALK, plays crucial roles in the pathogenesis of these tumors. Patients with ALK+ALCL are typically treated with combination chemotherapy containing doxorubicin. ALK+ALCL represents the second most common pediatric lymphoid cancer. The prognosis of pediatric patients is far better than that of adult patients. Dien Bard et al. have shown that IL-22 secreted by ALK+ALCL lymphoma cells stimulates STAT3 activation and the growth of these cells. Blocking the IL-22 signaling pathway using an IL-22-neutralizing antibody has been shown to significantly decrease the growth of ALK+ALCL cells in-vitro. |
| Cytogenetics | t(2;5)(p23;q35) in most ALK+ALCL patients; other translocation variants have been described. |
| Hybrid/Mutated Gene | NPM-ALK |
| Abnormal Protein | NPM-ALK |
| Entity | ALK negative anaplastic large cell lymphoma (ALK-ALCL) |
| Disease | ALK-ALCL is a subtype of ALCL characterized by a strong and homogeneous expression of CD30. These cells don't express the ALK protein. ALK-ALCL has a less favourable prognosis than ALK+ALCL. Patients with ALK-ALCL are usually older than in ALK+ALCL, 58 versus 34 years, and present a male predominance. Patients are treated with standard CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone) chemotherapy. By subtractive genomic hybridization, Lamant et al. have identified that IL-22 transcript is over-expressed in ALK-ALCL when compared to ALK+ALCL. However, the authors did not investigate the biological significance of this observation. |
| Entity | Lung cancer |
| Disease | There are two major types of lung cancer. The non-small cell lung cancer (NSCLC) is the most common type of lung cancer and is divided into three major subtypes: squamous cell carcinoma, adenocarcinoma and large cell carcinoma. Small cell lung cancer represents the second type of lung cancer and is also subdivided in three different subgroups: small cell carcinoma, mixed small cell/large cell and combined small cell carcinoma. More than 90% of lung cancers in men, and at least 70% in women are directly caused by cigarette smoking. Treatment is dependent on the lung cancer type and may involve surgery, radiation therapy and chemotherapy. The overall survival after 5 years for men and women is less than 20%. Evidence from both in vivo and in vitro experiments implicates IL-22 as a player in the development of non-small cell lung carcinoma (NSCLC) (Zhang et al., 2008). The authors have demonstrated that NSCLC patients have high levels of IL-22 protein in their serum when compared to normal individuals. Moreover, in NSCLC cells exogenous addition of recombinant IL-22 cytokine induces pro-survival pathways, including STAT3 signaling, and increase cell proliferation. They have also showed that IL-22 protects cancer cells from serum starvation and chemotherapeutic drug-induced apoptosis. In a xenograft model of NSCLC they have showed that down-regulation of IL-22 production significantly decreases the volume of the lung tumors. |
| Entity | Vitiligo |
| Disease | Vitiligo is characterized by the loss skin pigmentation. It's a multifactorial and polygenic disease. There are two forms of vitiligo, the segmental and the non-segmental form that are related to the pattern of the lesion. The disease affects both men and women. Vitiligo has been associated with autoimmune and inflammatory disorders, but the exact origin and causes are unknown. There is no cure for vitiligo to date, but treatment is available to slow down the depigmentation. In a recent study by Rätsep et al., it has been demonstrated that IL-22 mRNA and protein levels are associated with the disease. The authors have suggested that IL-22 may induce the inflammation process at the origin of the destruction of the melanocyte leading to skin depigmentation. |
| Entity | Psoriasis |
| Note | Recently, Ma et al. have demonstrated in a mouse model of psoriasis, that IL-22 is a key player in the development of this disease. Antibodies that neutralized IL-22 were found to prevent the development of psoriasis-like disease, reducing thickening of the skin, inflammatory infiltrates, and expression of Th17 cytokines. On the other hand, injection of IL-22 into the skin of normal mice induced the expression of genes associated with the development of psoriasis-like lesions. These data have revealed a new and promising approach for the treatment of psoriasis by antagonizing IL-22 activity. |
| Bibliography |
| Epidemiology of vitiligo and associated autoimmune diseases in Caucasian probands and their families. |
| Alkhateeb A, Fain PR, Thody A, Bennett DC, Spritz RA. |
| Pigment Cell Res. 2003 Jun;16(3):208-14. |
| PMID 12753387 |
| Are Segmental and Non- Segmental Vitiligo Different Disease Entities? Clinical Profile of 1100 Vitiligo Patients. |
| Anbar TS, Abdel-Rahman AT, Ghannam S, Hosam El-Din W and El- Khayyat MA. |
| Egyptian Dermatology Online Journal. Dec 2006;2(2):3. |
| Aberrant expression of IL-22 receptor 1 and autocrine IL-22 stimulation contribute to tumorigenicity in ALK+ anaplastic large cell lymphoma. |
| Bard JD, Gelebart P, Anand M, Amin HM, Lai R. |
| Leukemia. 2008 Aug;22(8):1595-603. Epub 2008 May 29. |
| PMID 18509351 |
| Crystal structure of the IL-22/IL-22R1 complex and its implications for the IL-22 signaling mechanism. |
| Bleicher L, de Moura PR, Watanabe L, Colau D, Dumoutier L, Renauld JC, Polikarpov I. |
| FEBS Lett. 2008 Sep 3;582(20):2985-92. Epub 2008 Aug 7. |
| PMID 18675809 |
| Estimated Five-year Relative Survival Ratio (%) (and 95% Confidence Interval) for the Most Common Cancers by Sex, Canada excluding Quebec*, 2001-2003. |
| Canadian Cancer Society. |
| Canadian Cancer statistics 2008; Table 14: page 57. |
| Expression and regulation of IL-22 in the IL-17-producing CD4+ T lymphocytes. |
| Chung Y, Yang X, Chang SH, Ma L, Tian Q, Dong C. |
| Cell Res. 2006 Nov;16(11):902-7. |
| PMID 17088898 |
| Lung Cancer. |
| Fossella FV, Komaki R, Putnam JB Jr., Cox JD, Hong WK, Roth JA. |
| Springer; 1st edition (October 1, 2002). 328 pages. |
| IL-22, a Th1 cytokine that targets the pancreas and select other peripheral tissues. |
| Gurney AL. |
| Int Immunopharmacol. 2004 May;4(5):669-77. (REVIEW) |
| PMID 15120651 |
| Stage 3 immature human natural killer cells found in secondary lymphoid tissue constitutively and selectively express the TH 17 cytokine interleukin-22. |
| Hughes T, Becknell B, McClory S, Briercheck E, Freud AG, Zhang X, Mao H, Nuovo G, Yu J, Caligiuri MA. |
| Blood. 2009 Apr 23;113(17):4008-10. Epub 2009 Feb 24. |
| PMID 19244159 |
| IL-22 is expressed by Th17 cells in an IL-23-dependent fashion, but not required for the development of autoimmune encephalomyelitis. |
| Kreymborg K, Etzensperger R, Dumoutier L, Haak S, Rebollo A, Buch T, Heppner FL, Renauld JC, Becher B. |
| J Immunol. 2007 Dec 15;179(12):8098-104. |
| PMID 18056351 |
| Gene-expression profiling of systemic anaplastic large-cell lymphoma reveals differences based on ALK status and two distinct morphologic ALK+ subtypes. |
| Lamant L, de Reynies A, Duplantier MM, Rickman DS, Sabourdy F, Giuriato S, Brugieres L, Gaulard P, Espinos E, Delsol G. |
| Blood. 2007 Mar 1;109(5):2156-64. Epub 2006 Oct 31. |
| PMID 17077326 |
| 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. |
| Lejeune D, Dumoutier L, Constantinescu S, Kruijer W, Schuringa JJ, Renauld JC. |
| J Biol Chem. 2002 Sep 13;277(37):33676-82. Epub 2002 Jun 26. |
| PMID 12087100 |
| Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. |
| Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M, Fouser LA. |
| J Exp Med. 2006 Oct 2;203(10):2271-9. Epub 2006 Sep 18. |
| PMID 16982811 |
| IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation. |
| Ma HL, Liang S, Li J, Napierata L, Brown T, Benoit S, Senices M, Gill D, Dunussi-Joannopoulos K, Collins M, Nickerson-Nutter C, Fouser LA, Young DA. |
| J Clin Invest. 2008 Feb;118(2):597-607. |
| PMID 18202747 |
| Gene expression study of IL10 family genes in vitiligo skin biopsies, peripheral blood mononuclear cells and sera. |
| Ratsep R, Kingo K, Karelson M, Reimann E, Raud K, Silm H, Vasar E, Koks S. |
| Br J Dermatol. 2008 Dec;159(6):1275-81. Epub 2008 Aug 19. |
| PMID 18717682 |
| ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project. |
| Savage KJ, Harris NL, Vose JM, Ullrich F, Jaffe ES, Connors JM, Rimsza L, Pileri SA, Chhanabhai M, Gascoyne RD, Armitage JO, Weisenburger DD; International Peripheral T-Cell Lymphoma Project. |
| Blood. 2008 Jun 15;111(12):5496-504. Epub 2008 Apr 2. |
| PMID 18385450 |
| Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22. |
| Takatori H, Kanno Y, Watford WT, Tato CM, Weiss G, Ivanov II, Littman DR, O'Shea JJ. |
| J Exp Med. 2009 Jan 16;206(1):35-41. Epub 2008 Dec 29. |
| PMID 19114665 |
| Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells. |
| Trifari S, Kaplan CD, Tran EH, Crellin NK, Spits H. |
| Nat Immunol. 2009 Aug;10(8):864-71. Epub 2009 Jul 5. |
| PMID 19578368 |
| IL-22-mediated tumor growth reduction correlates with inhibition of ERK1/2 and AKT phosphorylation and induction of cell cycle arrest in the G2-M phase. |
| Weber GF, Gaertner FC, Erl W, Janssen KP, Blechert B, Holzmann B, Weighardt H, Essler M. |
| J Immunol. 2006 Dec 1;177(11):8266-72. |
| PMID 17114505 |
| Cancer of the Lung: From Molecular Biology to Treatment Guidelines. |
| Weitberg AB. |
| Humana Press; 1st edition (January 15, 2002). 344 pages. |
| Interleukin-22: a novel T- and NK-cell derived cytokine that regulates the biology of tissue cells. |
| Wolk K, Sabat R. |
| Cytokine Growth Factor Rev. 2006 Oct;17(5):367-80. Epub 2006 Oct 9. (REVIEW) |
| PMID 17030002 |
| The Th17 cytokine IL-22 induces IL-20 production in keratinocytes: a novel immunological cascade with potential relevance in psoriasis. |
| Wolk K, Witte E, Warszawska K, Schulze-Tanzil G, Witte K, Philipp S, Kunz S, Docke WD, Asadullah K, Volk HD, Sterry W, Sabat R. |
| Eur J Immunol. 2009 Dec;39(12):3570-81. |
| PMID 19830738 |
| Antiapoptotic activity of autocrine interleukin-22 and therapeutic effects of interleukin-22-small interfering RNA on human lung cancer xenografts. |
| Zhang W, Chen Y, Wei H, Zheng C, Sun R, Zhang J, Tian Z. |
| Clin Cancer Res. 2008 Oct 15;14(20):6432-9. |
| PMID 18927282 |
| The interleukin-22/STAT3 pathway potentiates expression of inducible nitric-oxide synthase in human colon carcinoma cells. |
| Ziesche E, Bachmann M, Kleinert H, Pfeilschifter J, Muhl H. |
| J Biol Chem. 2007 Jun 1;282(22):16006-15. Epub 2007 Apr 16. |
| PMID 17438334 |
| Citation |
| This paper should be referenced as such : |
| Gelebart, P ; Lai, R |
| IL22 (interleukin 22) |
| Atlas Genet Cytogenet Oncol Haematol. 2011;15(2):187-190. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/IL22ID44519ch12q15.html |
| Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ] |
| Solid Tumors | TT_t0712p11q15ID107397 |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed Mar 11 18:12:03 CET 2020 |
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