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FLASH GENE
Symbol IL22 contributors: mct - updated : 09-04-2019
HGNC name interleukin 22
HGNC id 14900
Location 12q15      Physical location : 68.642.024 - 68.647.281
Synonym name
  • interleukin 21
  • IL10 related T cell derived inducible factor
  • cytokine Zcyto18
  • Synonym symbol(s) IL21, ILTIF, zcyto18, IL-TIF, IL-D110, TIFa, TIFIL-23, IL-22, IL-D110, MGC79382, MGC79384
    DNA
    TYPE functioning gene
    STRUCTURE 5.26 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure
  • IL22 promoter contains a putative conserved hypoxic response element suggesting that the transcription factor HIF1A may influence IL22 expression
  • MAPPING cloned Y linked N status provisional
    Physical map
    IRAK3 12q13.13 interleukin-1 receptor-associated kinase 3 RBMS1P 12q14.2 RNA binding motif, single stranded interacting protein 1, pseudogene LOC387866 12 LOC387866 LOC390340 12 similar to IAP-associated factor VIAF1; phosducin-like 2 HELB 12q14.2 helicase (DNA) B GRIP1 12q14.1-q14.2 glutamate receptor interacting protein 1 HGT2 12q14.3 glutamate receptor interacting protein 1 TIP120A 12q14 glutamate receptor interacting protein 1 LOC390341 12 similar to nuclear localization signal containing protein deleted in Velo-Cardio-Facial syndrome DYRK2 12q14.3 dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 2 LOC341333 12q14.3 similar to Heterogeneous nuclear ribonucleoprotein A1 (Helix-destabilizing protein) (Single-strand binding protein) (hnRNP core protein A1) IFNG 12q14-q15 interferon, gamma IL26 12q15 interleukin 26 IL22 12q15 interleukin 22 MDM1 12q14.3 nuclear protein double minute 1 LOC160410 12q14.3 proteasome (prosome, macropain) 26S subunit, ATPase, 6 pseudogene LOC387867 12 similar to 40S ribosomal protein SA (P40) (34/67 kDa laminin receptor) (Colon carcinoma laminin-binding protein) (NEM/1CHD4) (Multidrug resistance-associated protein MGr1-Ag) RAP1B 12q14 RAP1B, member of RAS oncogene family LOC246723 12q14 ATP synthase, H+ transporting, mitochondrial F0 complex, subunit d pseudogene NUP107 12q14.3 nuclear pore complex protein SLC35E3 12q15 solute carrier family 35, member E2 PRO2268 12q14.3 hypothetical protein PRO2268 MDM2 12q14.3-q15 Mdm2, transformed 3T3 cell double minute 2, p53 binding protein (mouse) MGC5370 12q14.3 hypothetical protein MGC5370 CPM 12q15 carboxypeptidase M CPSF6 12q13.2 cleavage and polyadenylation specific factor 6, 68kDa LYZ 12q14-q15 lysozyme (renal amyloidosis) GAS41 12q13-q15 lysozyme (renal amyloidosis) FRS2 12q15 fibroblast growth factor receptor substrate 2 CCT2 12q15 chaperonin containing TCP1, subunit 2 (beta) LOC387868 12 similar to leucine-rich repeat-containing 10; leucine-rich repeat protein; leucine-rich containing 10 VMD2L3 12q14.2-q15 similar to leucine-rich repeat-containing 10; leucine-rich repeat protein; leucine-rich containing 10 MGC13168 12q14.3 hypothetical protein MGC13168 RAB3IP 12q13-q15 RAB3A interacting protein (rabin3) FLJ25056 12q14.3 hypothetical protein FLJ25056
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 1147 19.9 179 - 2000 10954742
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Skin/Tegumentskin     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immuneactivated B lymphocyte
    Lymphoid/ImmuneT cell Homo sapiens
    not specificmast cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    interspecies homolog to murine Iltif
    Homologene
    FAMILY
  • interleukin (IL-10) family
  • CATEGORY immunity/defense , signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • has both proinflammatory and tissue-protective properties depending on the context in which it is expressed
  • IL10 and IL22 are crucial regulators of inflammation during immune responses, and IL22 elicits innate responses from tissue epithelia and promotes wound healing
  • regulates host immune responses to extracellular pathogens
  • IL22 and IL22RA2 are regulated during intestinal tissue damage
  • IL22 promotes the growth of pulmonary vascular smooth muscle cells (SMCs) via a signaling mechanism that involves NADPH oxidase-dependent oxidation
  • mast cells are major IL22 producers in patients with psoriasis and atopic dermatitis
  • IL22 may play a protective role in the development of vasculitis
  • is produced exclusively by immune cells and activates signal transducer and activator of transcription 3 (STAT3) in nonimmune cells, such as hepatocytes, keratinocytes, and colonic epithelial cells
  • exert beneficial effects on insulin secretion and to protect pancreatic beta-cells from stress
  • IL22 is produced by different cells in both innate and acquired immunities
  • has important functions in host defense at mucosal surfaces as well as in tissue repair
  • is involved in the development of lymphocytes and serves as a rapid and early source of the effector cytokines that are released in response to pathogen-induced changes in the microenvironment
  • plays an important role in cancer carcinogenesis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS inflammation
    PATHWAY
    metabolism
    signaling
  • IL22 signaling pathway orchestrates mucosal immune defense and tissue regeneration through pleiotropic effects including pro-survival signaling, cell migration, dysplasia and angiogenesis
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • IL17A can regulate the expression, proinflammatory properties, and tissue-protective functions of IL22, and indicate that the presence or absence of IL17A governs the proinflammatory versus tissue-protective properties of IL22 in a model of airway damage and inflammation
  • IL26 is often co-expressed with IL22 by activated T cells, especially Th17 cells
  • role of GAB1 and GAB2 in IL22-mediated keratinocyte proliferation, migration, and differentiation
  • regulation of IL22RA2 is crucial to control the effects of IL22 during intestinal tissue damage and tumorigenesis
  • IL27 may suppress the production of IL22 by inducing the expression of SOCS1 in human CD4(+) T cells
  • IL22 secreted by decidual stromal cells (DSCs) and decidual natural killer (dNK) cells might promote the survival of trophoblasts and participate in the maintenance of pregnancy by binding to the IL22RA1
  • S100A12, S100A8, S100A9 has no direct effect on cholesterol efflux in macrophages, but rather promotes the secretion of IL22, which then directly reduces cholesterol efflux in macrophages by decreasing the expression of ABCG1
  • IL21 is an inducer of IL22 production in CD4+ T cells
  • the role of the IL22/IL22RA1 axis in cancer is complex and context-specific
  • new functions for IKZF1 in maintaining mucosal immune homeostasis by restricting IL22 production by CD4(+) T cells
  • IL22 induces IL18 expression from epithelial cells during intestinal infection
  • in the intestinal tract, IL22 activates STAT3 to promote intestinal epithelial cell (IEC) homeostasis and tissue healing
  • TYK2 protects against acute colitis in part by amplifying inflammation-induced epithelial IL22 signaling to STAT3
  • IL22RA2 is a soluble IL22 receptor, which antagonizes IL22 activity and has genetic associations with autoimmune diseases
  • IL22 plays likely a protective role in glucose-stimulated insulin secretion (GSIS) via the down-regulation of UCP2
  • increased expression of IL22RA1 promotes keratinocyte proliferation and pro-inflammatory cytokine production during UVB-induced skin inflammation, suggesting that UVB facilitates skin inflammation by increasing the responsiveness of keratinocytes to IL22
  • IL22 increases intestinal epithelial permeability by upregulating CLDN2 expression through the JAK/STAT pathway, suggesting the role of IL22 in the regulation and maintenance of the intestinal epithelial barrier
  • cell & other
    REGULATION
    induced by lipopolysaccharide
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    correlate with disease activity in patients with systemic lupus erythematosus
    constitutional       loss of function
    deficiency of IL22 might lead to delayed colonic repair and increased intestinal inflammation thereby promoting tumor development
    constitutional     --over  
    in giant cell arteritis, and affects viability and gene expression of arterial cells
    tumoral     --over  
    increased occurrence of IL22 may enhance myeloma proliferation and growth, and moreover, may participate in the mechanisms of immune deregulation
    Susceptibility
  • to malaria
  • to risk of cancer
  • to preeclampsia (PE)
  • Variant & Polymorphism other
  • two IL22 haplotypes that are, respectively, associated with resistance and susceptibility to malaria
  • rs1179251 polymorphism was associated with increased risk of cancer
  • IL22 rs2227485 may be associated with the development of preeclampsia (PE)
  • Candidate gene
    Marker
  • IL22 could be an important biomarker of inflammation in preeclampsia
  • Therapy target
    ANIMAL & CELL MODELS
  • Il22(-/-) mice were more resistant to lethal West Nile virus (WNV) encephalitis, but had similar viral loads in the periphery compared to wild type (WT) mice