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IL22 (interleukin 22)

Written2010-05Pascal Gelebart, Raymond Lai
Department of Laboratory Medicine, Pathology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)ILTIF
IL-21
zcyto18
IL-TIF
IL-D110
TIFa
TIFIL-23
IL-22
MGC79382
MGC79384
Other aliasIL21
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

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PMID 12753387
 
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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.
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FEBS Lett. 2008 Sep 3;582(20):2985-92. Epub 2008 Aug 7.
PMID 18675809
 
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Canadian Cancer Society.
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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.
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PMID 17088898
 
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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.
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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.
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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


External links

Nomenclature
HGNC (Hugo)IL22   14900
Cards
AtlasIL22ID44519ch12q15
Entrez_Gene (NCBI)IL22  50616  interleukin 22
AliasesIL-21; IL-22; IL-D110; IL-TIF; 
ILTIF; TIFIL-23; TIFa; zcyto18
GeneCards (Weizmann)IL22
Ensembl hg19 (Hinxton)ENSG00000127318 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000127318 [Gene_View]  chr12:68248245-68253501 [Contig_View]  IL22 [Vega]
ICGC DataPortalENSG00000127318
TCGA cBioPortalIL22
AceView (NCBI)IL22
Genatlas (Paris)IL22
WikiGenes50616
SOURCE (Princeton)IL22
Genetics Home Reference (NIH)IL22
Genomic and cartography
GoldenPath hg38 (UCSC)IL22  -     chr12:68248245-68253501 -  12q15   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)IL22  -     12q15   [Description]    (hg19-Feb_2009)
EnsemblIL22 - 12q15 [CytoView hg19]  IL22 - 12q15 [CytoView hg38]
Mapping of homologs : NCBIIL22 [Mapview hg19]  IL22 [Mapview hg38]
OMIM605330   
Gene and transcription
Genbank (Entrez)AF279437 AJ277247 AY358890 BC066263 BC066264
RefSeq transcript (Entrez)NM_020525
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)IL22
Cluster EST : UnigeneHs.287369 [ NCBI ]
CGAP (NCI)Hs.287369
Alternative Splicing GalleryENSG00000127318
Gene ExpressionIL22 [ NCBI-GEO ]   IL22 [ EBI - ARRAY_EXPRESS ]   IL22 [ SEEK ]   IL22 [ MEM ]
Gene Expression Viewer (FireBrowse)IL22 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)50616
GTEX Portal (Tissue expression)IL22
Human Protein AtlasENSG00000127318-IL22 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9GZX6   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9GZX6  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9GZX6
Splice isoforms : SwissVarQ9GZX6
PhosPhoSitePlusQ9GZX6
Domaine pattern : Prosite (Expaxy)INTERLEUKIN_10 (PS00520)   
Domains : Interpro (EBI)4_helix_cytokine-like_core    4_helix_cytokine_core    IL-10_CS    IL-22   
Domain families : Pfam (Sanger)IL22 (PF14565)   
Domain families : Pfam (NCBI)pfam14565   
Conserved Domain (NCBI)IL22
DMDM Disease mutations50616
Blocks (Seattle)IL22
PDB (SRS)1M4R    1YKB    3DGC    3DLQ    3G9V    3Q1S   
PDB (PDBSum)1M4R    1YKB    3DGC    3DLQ    3G9V    3Q1S   
PDB (IMB)1M4R    1YKB    3DGC    3DLQ    3G9V    3Q1S   
PDB (RSDB)1M4R    1YKB    3DGC    3DLQ    3G9V    3Q1S   
Structural Biology KnowledgeBase1M4R    1YKB    3DGC    3DLQ    3G9V    3Q1S   
SCOP (Structural Classification of Proteins)1M4R    1YKB    3DGC    3DLQ    3G9V    3Q1S   
CATH (Classification of proteins structures)1M4R    1YKB    3DGC    3DLQ    3G9V    3Q1S   
SuperfamilyQ9GZX6
Human Protein Atlas [tissue]ENSG00000127318-IL22 [tissue]
Peptide AtlasQ9GZX6
HPRD05621
IPIIPI00008372   
Protein Interaction databases
DIP (DOE-UCLA)Q9GZX6
IntAct (EBI)Q9GZX6
FunCoupENSG00000127318
BioGRIDIL22
STRING (EMBL)IL22
ZODIACIL22
Ontologies - Pathways
QuickGOQ9GZX6
Ontology : AmiGOcytokine activity  protein binding  extracellular region  extracellular region  extracellular space  acute-phase response  inflammatory response  cell-cell signaling  interleukin-22 receptor binding  response to glucocorticoid  
Ontology : EGO-EBIcytokine activity  protein binding  extracellular region  extracellular region  extracellular space  acute-phase response  inflammatory response  cell-cell signaling  interleukin-22 receptor binding  response to glucocorticoid  
Pathways : KEGGCytokine-cytokine receptor interaction    Jak-STAT signaling pathway    Inflammatory bowel disease (IBD)   
REACTOMEQ9GZX6 [protein]
REACTOME PathwaysR-HSA-8854691 [pathway]   
NDEx NetworkIL22
Atlas of Cancer Signalling NetworkIL22
Wikipedia pathwaysIL22
Orthology - Evolution
OrthoDB50616
GeneTree (enSembl)ENSG00000127318
Phylogenetic Trees/Animal Genes : TreeFamIL22
HOVERGENQ9GZX6
HOGENOMQ9GZX6
Homologs : HomoloGeneIL22
Homology/Alignments : Family Browser (UCSC)IL22
Gene fusions - Rearrangements
Fusion : MitelmanVOPP1/IL22 [7p11.2/12q15]  [t(7;12)(p11;q15)]  
Tumor Fusion PortalIL22
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerIL22 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)IL22
dbVarIL22
ClinVarIL22
1000_GenomesIL22 
Exome Variant ServerIL22
ExAC (Exome Aggregation Consortium)ENSG00000127318
GNOMAD BrowserENSG00000127318
Genetic variants : HAPMAP50616
Genomic Variants (DGV)IL22 [DGVbeta]
DECIPHERIL22 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisIL22 
Mutations
ICGC Data PortalIL22 
TCGA Data PortalIL22 
Broad Tumor PortalIL22
OASIS PortalIL22 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICIL22  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDIL22
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch IL22
DgiDB (Drug Gene Interaction Database)IL22
DoCM (Curated mutations)IL22 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)IL22 (select a term)
intoGenIL22
NCG5 (London)IL22
Cancer3DIL22(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM605330   
Orphanet
DisGeNETIL22
MedgenIL22
Genetic Testing Registry IL22
NextProtQ9GZX6 [Medical]
TSGene50616
GENETestsIL22
Target ValidationIL22
Huge Navigator IL22 [HugePedia]
snp3D : Map Gene to Disease50616
BioCentury BCIQIL22
ClinGenIL22
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD50616
Chemical/Pharm GKB GenePA29822
Clinical trialIL22
Miscellaneous
canSAR (ICR)IL22 (select the gene name)
Probes
Litterature
PubMed244 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineIL22
EVEXIL22
GoPubMedIL22
iHOPIL22
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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