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Interleukin 22

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Title: Interleukin 22  
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Interleukin 22

Interleukin 22
Crystallographic structure of IL-22 (rainbow colored, N-terminus = blue, C-terminus = red) complexed with the IL-22R1 (magenta).[1]
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols  ; IL-21; IL-22; IL-D110; IL-TIF; ILTIF; TIFIL-23; TIFa; zcyto18
External IDs GeneCards:
Species Human Mouse
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

Interleukin-22 (IL-22) is protein that in humans is encoded by the IL22 gene.[2][3]


  • Structure 1
  • Function 2
  • Target tissue 3
  • Signaling 4
  • References 5
  • Further reading 6


IL-22 is an α-helical cytokine. IL-22 binds to a heterodimeric cell surface receptor composed of IL-10R2 and IL-22R1 subunits.[4] IL-22R is expressed on tissue cells, and it is absent on immune cells.[5]

Crystallization is possible if the N-linked glycosylation sites are removed in mutants of IL-22 bound with high-affinity cell-surface receptor sIL-22R1. The crystallographic asymmetric unit contained two IL-22-sIL-22R1 complexes.[4]


IL-22 a member of a group of cytokines called the IL-10 family or IL-10 superfamily (including IL-19, IL-20, IL-24, and IL-26),[6] a class of potent mediators of cellular inflammatory responses. It shares use of IL-10R2 in cell signaling with other members of this family, IL-10, IL-26, IL-28A/B and IL-29.[7] IL-22 is produced by activated DC and T cells and initiates innate immune responses against bacterial pathogens especially in epithelial cells such as respiratory and gut epithelial cells. IL-22 along with IL-17 is rapidly produced by splenic LTi-like cells [8] and also produced by Th17 cells and likely plays a role in the coordinated response of both adaptive innate immune systems, autoimmunity and tissue regeneration.[9]

IL-22 biological activity is initiated by binding to a cell-surface complex composed of IL-22R1 and IL-10R2 receptor chains and further regulated by interactions with a soluble binding protein, IL-22BP, which shares sequence similarity with an extracellular region of IL-22R1 (sIL-22R1). IL-22 and IL-10 receptor chains play a role in cellular targeting and signal transduction to selectively initiate and regulate immune responses.[4] IL-22 can contribute to immune disease through the stimulation of inflammatory responses, S100s and defensins. IL-22 also promotes hepatocyte survival in the liver and epithelial cells in the lung and gut similar to IL-10.[10] In some contexts, the pro-inflammatory versus tissue-protective functions of IL-22 are regulated by the often co-expressed cytokine IL-17A [11]

Target tissue

Targets of this cytokine are mostly non-hematopoietic cells such as hepatocytes, keratinocytes, and lung and intestinal epithelial cells. Pancreatic islets also express high levels of IL-22 receptor. It has been shown to induce islet beta cell regeneration.[12]


IL-22, signals through the interferon receptor-related proteins CRF2-4 and IL-22R.[3] It forms cell surface complexes with IL-22R1 and IL-10R2 chains resulting in signal transduction through receptor, IL-10R2. The IL-22/IL-22R1/IL-10R2 complex activates intracellular kinases (JAK1, Tyk2, and MAP kinases) and transcription factors, especially STAT3. It can induce IL-20 and IL-24 signaling when IL-22R1 pairs with IL-20R2.


  1. ^ ​; Jones BC, Logsdon NJ, Walter MR (September 2008). "Structure of IL-22 bound to its high-affinity IL-22R1 chain". Structure 16 (9): 1333–44.  
  2. ^ Dumoutier L, Van Roost E, Colau D, Renauld JC (Aug 2000). "Human interleukin-10-related T cell-derived inducible factor: molecular cloning and functional characterization as an hepatocyte-stimulating factor". Proceedings of the National Academy of Sciences of the United States of America 97 (18): 10144–9.  
  3. ^ a b Xie MH, Aggarwal S, Ho WH, Foster J, Zhang Z, Stinson J, Wood WI, Goddard AD, Gurney AL (Oct 2000). "Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R". The Journal of Biological Chemistry 275 (40): 31335–9.  
  4. ^ a b c ​; Jones BC, Logsdon NJ, Walter MR (Sep 2008). "Structure of IL-22 bound to its high-affinity IL-22R1 chain". Structure 16 (9): 1333–44.  
  5. ^ Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R (Aug 2004). "IL-22 increases the innate immunity of tissues". Immunity 21 (2): 241–54.  
  6. ^ Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher PB (2004). "Interleukin-10 and related cytokines and receptors". Annual Review of Immunology 22: 929–79.  
  7. ^ Witte K, Witte E, Sabat R, Wolk K (Aug 2010). "IL-28A, IL-28B, and IL-29: promising cytokines with type I interferon-like properties". Cytokine & Growth Factor Reviews 21 (4): 237–51.  
  8. ^ Takatori H, Kanno Y, Watford WT, Tato CM, Weiss G, Ivanov II, Littman DR, O'Shea JJ (Jan 2009). "Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22". The Journal of Experimental Medicine 206 (1): 35–41.  
  9. ^ Nikoopour E, Bellemore SM, Singh B (Jul 2015). "IL-22, cell regeneration and autoimmunity". Cytokine 74 (1): 35–42.  
  10. ^ Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A (2001). "Interleukin-10 and the interleukin-10 receptor". Annual Review of Immunology 19: 683–765.  .
  11. ^ Sonnenberg GF, Nair MG, Kirn TJ, Zaph C, Fouser LA, Artis D (Jun 2010). "Pathological versus protective functions of IL-22 in airway inflammation are regulated by IL-17A". The Journal of Experimental Medicine 207 (6): 1293–305.  
  12. ^ Hill T, Krougly O, Nikoopour E, Bellemore S, Lee-Chan E, Fouser LA, Hill DJ, Singh B (2013). "The involvement of interleukin-22 in the expression of pancreatic beta cell regenerative Reg genes". Cell Regeneration 2 (1): 2.  

Further reading

  • Weger W, Hofer A, Wolf P, El-Shabrawi Y, Renner W, Kerl H, Salmhofer W (Sep 2009). "Common polymorphisms in the interleukin-22 gene are not associated with chronic plaque psoriasis". Experimental Dermatology 18 (9): 796–8.  
  • Davila S, Froeling FE, Tan A, Bonnard C, Boland GJ, Snippe H, Hibberd ML, Seielstad M (Apr 2010). "New genetic associations detected in a host response study to hepatitis B vaccine". Genes and Immunity 11 (3): 232–8.  
  • Silverberg MS, Cho JH, Rioux JD, McGovern DP, Wu J, Annese V, Achkar JP, Goyette P, Scott R, Xu W, Barmada MM, Klei L, Daly MJ, Abraham C, Bayless TM, Bossa F, Griffiths AM, Ippoliti AF, Lahaie RG, Latiano A, Paré P, Proctor DD, Regueiro MD, Steinhart AH, Targan SR, Schumm LP, Kistner EO, Lee AT, Gregersen PK, Rotter JI, Brant SR, Taylor KD, Roeder K, Duerr RH (Feb 2009). "Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study". Nature Genetics 41 (2): 216–20.  
  • de Moura PR, Watanabe L, Bleicher L, Colau D, Dumoutier L, Lemaire MM, Renauld JC, Polikarpov I (Apr 2009). "Crystal structure of a soluble decoy receptor IL-22BP bound to interleukin-22". FEBS Letters 583 (7): 1072–7.  
  • Wong CK, Lun SW, Ko FW, Wong PT, Hu SQ, Chan IH, Hui DS, Lam CW (2009). "Activation of peripheral Th17 lymphocytes in patients with asthma". Immunological Investigations 38 (7): 652–64.  
  • Shen H, Goodall JC, Hill Gaston JS (Jun 2009). "Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis". Arthritis and Rheumatism 60 (6): 1647–56.  
  • Thompson CL, Plummer SJ, Tucker TC, Casey G, Li L (Aug 2010). "Interleukin-22 genetic polymorphisms and risk of colon cancer". Cancer Causes & Control 21 (8): 1165–70.  
  • Hughes T, Becknell B, McClory S, Briercheck E, Freud AG, Zhang X, Mao H, Nuovo G, Yu J, Caligiuri MA (Apr 2009). "Stage 3 immature human natural killer cells found in secondary lymphoid tissue constitutively and selectively express the TH 17 cytokine interleukin-22". Blood 113 (17): 4008–10.  
  • Siezen CL, Bont L, Hodemaekers HM, Ermers MJ, Doornbos G, Van't Slot R, Wijmenga C, Houwelingen HC, Kimpen JL, Kimman TG, Hoebee B, Janssen R (Apr 2009). "Genetic susceptibility to respiratory syncytial virus bronchiolitis in preterm children is associated with airway remodeling genes and innate immune genes". The Pediatric Infectious Disease Journal 28 (4): 333–5.  
  • Pitta MG, Romano A, Cabantous S, Henri S, Hammad A, Kouriba B, Argiro L, el Kheir M, Bucheton B, Mary C, El-Safi SH, Dessein A (Aug 2009). "IL-17 and IL-22 are associated with protection against human kala azar caused by Leishmania donovani". The Journal of Clinical Investigation 119 (8): 2379–87.  
  • Pan HF, Zhao XF, Yuan H, Zhang WH, Li XP, Wang GH, Wu GC, Tang XW, Li WX, Li LH, Feng JB, Hu CS, Ye DQ (Mar 2009). "Decreased serum IL-22 levels in patients with systemic lupus erythematosus". Clinica Chimica Acta; International Journal of Clinical Chemistry 401 (1-2): 179–80.  
  • Liu Y, Yang B, Zhou M, Li L, Zhou H, Zhang J, Chen H, Wu C (Jun 2009). "Memory IL-22-producing CD4+ T cells specific for Candida albicans are present in humans". European Journal of Immunology 39 (6): 1472–9.  
  • Sekikawa A, Fukui H, Suzuki K, Karibe T, Fujii S, Ichikawa K, Tomita S, Imura J, Shiratori K, Chiba T, Fujimori T (Mar 2010). "Involvement of the IL-22/REG Ialpha axis in ulcerative colitis". Laboratory Investigation; A Journal of Technical Methods and Pathology 90 (3): 496–505.  
  • He M, Liang P (Feb 2010). "IL-24 transgenic mice: in vivo evidence of overlapping functions for IL-20, IL-22, and IL-24 in the epidermis". Journal of Immunology 184 (4): 1793–8.  
  • Wolk K, Witte E, Warszawska K, Schulze-Tanzil G, Witte K, Philipp S, Kunz S, Döcke WD, Asadullah K, Volk HD, Sterry W, Sabat R (Dec 2009). "The Th17 cytokine IL-22 induces IL-20 production in keratinocytes: a novel immunological cascade with potential relevance in psoriasis". European Journal of Immunology 39 (12): 3570–81.  
  • Eyerich S, Eyerich K, Pennino D, Carbone T, Nasorri F, Pallotta S, Cianfarani F, Odorisio T, Traidl-Hoffmann C, Behrendt H, Durham SR, Schmidt-Weber CB, Cavani A (Dec 2009). "Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling". The Journal of Clinical Investigation 119 (12): 3573–85.  
  • Dhiman R, Indramohan M, Barnes PF, Nayak RC, Paidipally P, Rao LV, Vankayalapati R (Nov 2009). "IL-22 produced by human NK cells inhibits growth of Mycobacterium tuberculosis by enhancing phagolysosomal fusion". Journal of Immunology 183 (10): 6639–45.  
  • Cella M, Fuchs A, Vermi W, Facchetti F, Otero K, Lennerz JK, Doherty JM, Mills JC, Colonna M (Feb 2009). "A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity". Nature 457 (7230): 722–5.  
  • Sanjabi S, Zenewicz LA, Kamanaka M, Flavell RA (Aug 2009). "Anti-inflammatory and pro-inflammatory roles of TGF-beta, IL-10, and IL-22 in immunity and autoimmunity". Current Opinion in Pharmacology 9 (4): 447–53.  
  • Kagami S, Rizzo HL, Lee JJ, Koguchi Y, Blauvelt A (May 2010). "Circulating Th17, Th22, and Th1 cells are increased in psoriasis". The Journal of Investigative Dermatology 130 (5): 1373–83.  
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