IL22 (interleukin 22)

2010-05-01   Pascal Gelebart , Raymond Lai 

Department of Laboratory Medicine, Pathology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada




Atlas Image
Representation of the IL22 gene organization. Interleukin 22 gene and RNA structure.


The gene spans a region of 5.2 kb and the coding part is divided into five exons.


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.


None described so far.


Atlas Image
Crystal structure of IL-22 at 2.6 A resolution. Adapted from PDB (access number: 1YKB).


IL-22 is a cytokine composed of 179 residues.


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.


IL-22 is a secreted protein.


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.



No mutation has been reported thus far.

Implicated in

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.
t(2;5)(p23;q35) in most ALK+ALCL patients; other translocation variants have been described.
Hybrid gene
Fusion protein
ALK-ALCL is a subtype of ALCL characterized by a strong and homogeneous expression of CD30. These cells dont 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 name
Lung cancer
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 name
Vitiligo is characterized by the loss skin pigmentation. Its 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 name
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.


Pubmed IDLast YearTitleAuthors
127533872003Epidemiology of vitiligo and associated autoimmune diseases in Caucasian probands and their families.Alkhateeb A et al
185093512008Aberrant expression of IL-22 receptor 1 and autocrine IL-22 stimulation contribute to tumorigenicity in ALK+ anaplastic large cell lymphoma.Bard JD et al
186758092008Crystal structure of the IL-22/IL-22R1 complex and its implications for the IL-22 signaling mechanism.Bleicher L et al
170888982006Expression and regulation of IL-22 in the IL-17-producing CD4+ T lymphocytes.Chung Y et al
151206512004IL-22, a Th1 cytokine that targets the pancreas and select other peripheral tissues.Gurney AL et al
192441592009Stage 3 immature human natural killer cells found in secondary lymphoid tissue constitutively and selectively express the TH 17 cytokine interleukin-22.Hughes T et al
180563512007IL-22 is expressed by Th17 cells in an IL-23-dependent fashion, but not required for the development of autoimmune encephalomyelitis.Kreymborg K et al
170773262007Gene-expression profiling of systemic anaplastic large-cell lymphoma reveals differences based on ALK status and two distinct morphologic ALK+ subtypes.Lamant L et al
120871002002Interleukin-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 et al
169828112006Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides.Liang SC et al
182027472008IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation.Ma HL et al
187176822008Gene expression study of IL10 family genes in vitiligo skin biopsies, peripheral blood mononuclear cells and sera.Rätsep R et al
183854502008ALK- 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 et al
191146652009Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22.Takatori H et al
195783682009Identification 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 et al
171145052006IL-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 et al
170300022006Interleukin-22: a novel T- and NK-cell derived cytokine that regulates the biology of tissue cells.Wolk K et al
198307382009The Th17 cytokine IL-22 induces IL-20 production in keratinocytes: a novel immunological cascade with potential relevance in psoriasis.Wolk K et al
189272822008Antiapoptotic activity of autocrine interleukin-22 and therapeutic effects of interleukin-22-small interfering RNA on human lung cancer xenografts.Zhang W et al
174383342007The interleukin-22/STAT3 pathway potentiates expression of inducible nitric-oxide synthase in human colon carcinoma cells.Ziesché E et al

Other Information

Locus ID:

NCBI: 50616
MIM: 605330
HGNC: 14900
Ensembl: ENSG00000127318


dbSNP: 50616
ClinVar: 50616
TCGA: ENSG00000127318


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Cytokine-cytokine receptor interactionKEGGko04060
Jak-STAT signaling pathwayKEGGko04630
Cytokine-cytokine receptor interactionKEGGhsa04060
Jak-STAT signaling pathwayKEGGhsa04630
Inflammatory bowel disease (IBD)KEGGhsa05321
Inflammatory bowel disease (IBD)KEGGko05321
Immune SystemREACTOMER-HSA-168256
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Interleukin-19, 20, 22, 24REACTOMER-HSA-8854691
Th17 cell differentiationKEGGko04659
Th17 cell differentiationKEGGhsa04659


Pubmed IDYearTitleCitations
182641102008IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia.476
189787712009A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity.450
199203552009Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling.291
151227622004Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation.207
165379742006IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and intestinal epithelial cell migration.191
120871002002Interleukin-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-10.151
161431352005Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts.151
200329932010Circulating Th17, Th22, and Th1 cells are increased in psoriasis.145
194798692009Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis.140
234058992013IL-22, not simply a Th17 cytokine.134


Pascal Gelebart ; Raymond Lai

IL22 (interleukin 22)

Atlas Genet Cytogenet Oncol Haematol. 2010-05-01

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