Gene Symbol: IL22RA2
Description: interleukin 22 receptor subunit alpha 2
Alias: CRF2-10, CRF2-S1, CRF2X, IL-22BP, IL-22R-alpha-2, IL-22RA2, ZCYTOR16, interleukin-22 receptor subunit alpha-2, cytokine receptor class-II member 10, cytokine receptor family type 2, soluble 1, interleukin 22 receptor, alpha 2, interleukin 22-binding protein
Species: human
Products:     IL22RA2

Top Publications

  1. Huo H, Chen S, Li L, Laghari Z, Li N, Nie P. Functional characterization of interleukin (IL)-22 and its inhibitor, IL-22 binding protein (IL-22BP) in Mandarin fish, Siniperca chuatsi. Dev Comp Immunol. 2019;97:88-97 pubmed publisher
    ..In conclusion, the mandarin fish IL-22 and IL-22BP are conserved in their interaction and function with their mammalian orthologues, and these findings provide basis for future research on IL-22-IL-22BP axis in fish immunity. ..
  2. Conklin L, Merkel P, Pachman L, Parikh H, Tawalbeh S, Damsker J, et al. Serum biomarkers of glucocorticoid response and safety in anti-neutrophil cytoplasmic antibody-associated vasculitis and juvenile dermatomyositis. Steroids. 2018;140:159-166 pubmed publisher
    ..Similarly, safety biomarkers may also be helpful assessing toxicity of alternatives to glucocorticoids. ..
  3. Tamehiro N, Nishida K, Sugita Y, Hayakawa K, Oda H, Nitta T, et al. Ras homolog gene family H (RhoH) deficiency induces psoriasis-like chronic dermatitis by promoting TH17 cell polarization. J Allergy Clin Immunol. 2018;: pubmed publisher
    ..Our results indicate that RhoH inhibits TH17 differentiation and thereby plays a role in the pathogenesis of psoriasis. Additionally, IL-22 binding protein has therapeutic potential for the treatment of psoriasis. ..
  4. Franklin K, Hauser S, Lasek A, McClintick J, Ding Z, McBride W, et al. Reduction of alcohol drinking of alcohol-preferring (P) and high-alcohol drinking (HAD1) rats by targeting phosphodiesterase-4 (PDE4). Psychopharmacology (Berl). 2015;232:2251-62 pubmed publisher
    ..This study evaluated the involvement of PDE4 and Il22ra2 on ethanol (EtOH) intake by alcohol-preferring (P) and high-alcohol-drinking (HAD1) rats...
  5. Couturier Maillard A, Froux N, Piotet Morin J, Michaudel C, Brault L, Le Bérichel J, et al. Interleukin-22-deficiency and microbiota contribute to the exacerbation of Toxoplasma gondii-induced intestinal inflammation. Mucosal Immunol. 2018;11:1181-1190 pubmed publisher
    ..In conclusion, IL-22 participates in T.gondii induced acute small intestinal inflammation independently of microbiota and Reg3γ. ..
  6. Chen H, Liu W, Wang B, Mao H, Sun Z, Hou Q, et al. Cloning, identification of the two cytokine receptor family B subunits CRFB1 and CRFB5 from grass carp (Ctenopharyngodon idella). Fish Shellfish Immunol. 2015;45:211-20 pubmed publisher
    ..This indicated that the homodimer and the heterodimer were the potential receptor for CiIFN. ..
  7. Le P, Pearce M, Zhang S, Campbell E, Fok C, Mueller E, et al. IL22 regulates human urothelial cell sensory and innate functions through modulation of the acetylcholine response, immunoregulatory cytokines and antimicrobial peptides: assessment of an in vitro model. PLoS ONE. 2014;9:e111375 pubmed publisher the mRNA level, both forms of the IL22 receptor, the membrane-associated (IL22RA1) and the secreted soluble (IL22RA2) forms; in turn, IL22 inhibited expression of MR1 and induced expression of CarAT and two antimicrobial peptides (..
  8. Ahn J, Konno H, Barber G. Diverse roles of STING-dependent signaling on the development of cancer. Oncogene. 2015;34:5302-8 pubmed publisher
    ..Our data indicate that STING constitutes a critical component of the host early response to intestinal damage and is essential for invigorating tissue repair pathways that may help prevent tumorigenesis. ..
  9. Kulakova O, Bashinskaya V, Kiselev I, Baulina N, Tsareva E, Nikolaev R, et al. Pharmacogenetics of glatiramer acetate therapy for multiple sclerosis: the impact of genome-wide association studies identified disease risk loci. Pharmacogenomics. 2017;18:1563-1574 pubmed publisher
    ..Alleles/genotypes of EOMES, CLEC16A, IL22RA2, PVT1 and HLA-DRB1 were associated by themselves with event-free phenotype during GA treatment for at least 2 ..

More Information


  1. Ciccia F, Guggino G, Rizzo A, Bombardieri M, Raimondo S, Carubbi F, et al. Interleukin (IL)-22 receptor 1 is over-expressed in primary Sjogren's syndrome and Sjögren-associated non-Hodgkin lymphomas and is regulated by IL-18. Clin Exp Immunol. 2015;181:219-29 pubmed publisher
    ..An IL-18-dependent aberrant expression of IL-22R1 on cells of haematopoietic origin seems to be a specific immunological signature of patients with pSS and pSS-associated lymphomas. ..
  2. Crnkovic S, Schmidt A, Egemnazarov B, Wilhelm J, Marsh L, Ghanim B, et al. Functional and molecular factors associated with TAPSE in hypoxic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2016;311:L59-73 pubmed publisher
    ..analysis identified two soluble factors, fibroblast growth factor-5 (FGF5) and interleukin-22 receptor alpha-2 (IL22RA2), as being possibly associated with RV remodeling...
  3. Ferrao R, Wallweber H, Ho H, Tam C, Franke Y, Quinn J, et al. The Structural Basis for Class II Cytokine Receptor Recognition by JAK1. Structure. 2016;24:897-905 pubmed publisher
    ..Together, these data identify a conserved JAK binding site for receptor peptides and elucidate the mechanism by which class II cytokine receptors interact with JAK1. ..
  4. Ratsimandresy R, Indramohan M, Dorfleutner A, Stehlik C. The AIM2 inflammasome is a central regulator of intestinal homeostasis through the IL-18/IL-22/STAT3 pathway. Cell Mol Immunol. 2017;14:127-142 pubmed publisher
    ..Collectively, our results demonstrate a central role for the AIM2 inflammasome in preventing dysbiosis and intestinal inflammation through regulation of the IL-18/IL-22BP/IL-22 and STAT3 pathway and expression of select AMPs. ..
  5. Brockmann L, Giannou A, Gagliani N, Huber S. Regulation of TH17 Cells and Associated Cytokines in Wound Healing, Tissue Regeneration, and Carcinogenesis. Int J Mol Sci. 2017;18: pubmed publisher
    ..cytokine of TH17 cells, can be controlled by an endogenous soluble inhibitory receptor, Interleukin 22 binding protein (IL-22BP)...
  6. Riedl T, van Boxtel E, Bosch M, Parren P, Gerritsen A. High-Throughput Screening for Internalizing Antibodies by Homogeneous Fluorescence Imaging of a pH-Activated Probe. J Biomol Screen. 2016;21:12-23 pubmed publisher
    ..Our method enables functional screening of large antibody libraries to identify therapeutic antibody candidates with internalization characteristics favorable for the development of ADCs. ..
  7. Voglis S, Moos S, Kloos L, Wanke F, Zayoud M, Pelczar P, et al. Regulation of IL-22BP in psoriasis. Sci Rep. 2018;8:5085 pubmed publisher
    ..We conclude that regulation of IL-22BP by inflammatory mediators is an important step for the progression of inflammation in the skin and possibly also in other autoimmune diseases. ..
  8. Wang K, Gao M, Yang M, Meng F, Li D, Lu R, et al. Transcriptome analysis of bronchoalveolar lavage fluid from children with severe Mycoplasma pneumoniae pneumonia reveals novel gene expression and immunodeficiency. Hum Genomics. 2017;11:4 pubmed publisher
    ..The top 10 most down-regulated genes were OSTN-AS1, IL22RA2, COL3A1, C1orf141, IGKV2-29, RP11-731F5.2, IGHV4-4, KIRREL, DNASE1L3, and COL6A2...
  9. Singh V, Singh L, Vasudevan M, Chattopadhyay I, Borthakar B, Rai A, et al. Esophageal Cancer Epigenomics and Integrome Analysis of Genome-Wide Methylation and Expression in High Risk Northeast Indian Population. OMICS. 2015;19:688-99 pubmed publisher
    ..CADM3, OMD, NEFM, FBN2, CTNNB1, DLX6, UGT2B4, CCDC80, PZP, SERPINA4, TNFSF13B, NPC1, COL1A1, TAC3, BMP8A, and IL22RA2) with promoter hypomethylation and upregulation...
  10. Pelczar P, Witkowski M, Perez L, Kempski J, Hammel A, Brockmann L, et al. A pathogenic role for T cell-derived IL-22BP in inflammatory bowel disease. Science. 2016;354:358-362 pubmed
    ..Our findings suggest that anti-TNF-? therapy may act at least in part by suppressing IL-22BP and point toward a more specific potential therapy for IBD. ..
  11. Hou W, Wang B, Zhou Y, Xu K, Meng L, Zhu W, et al. IL‑22 expression is increased variedly in the initial phase, onset and chronic phase of a pristane‑induced arthritis rat model. Mol Med Rep. 2017;16:1109-1116 pubmed publisher
    ..It is thought that IL‑22 may serve an important role in the pathological process of PIA, particularly in the chronic fluctuation phase. Therefore, it may be a candidate molecule for the treatment of rheumatoid arthritis. ..
  12. Yang S, Han F, Wu J, Zhao Z, Zhan W. Association between CXCR2 and IL-22BP expression indicate a poor outcome for gastric adenocarcinoma progression. Oncol Lett. 2016;12:1477-1484 pubmed
    ..The coexpression of CXCR2 and IL-22BP was demonstrated in GA, which may indicate that CXCR2 is involved in more complex mechanisms and roles, and indicate a poor outcome in GA progression. ..
  13. Li Y, Fan L, Tang T, Tang Y, Xie M, Zeng X, et al. Modified apple polysaccharide prevents colitis through modulating IL-22 and IL-22BP expression. Int J Biol Macromol. 2017;103:1217-1223 pubmed publisher
    ..These data may provide another molecular basis for understanding how apples act to prevent colitis and suggest that MAP has a potential to treat colitis and prevent CRC. ..
  14. Misiorek J, Lähdeniemi I, Nyström J, Paramonov V, Gullmets J, Saarento H, et al. Keratin 8-deletion induced colitis predisposes to murine colorectal cancer enforced by the inflammasome and IL-22 pathway. Carcinogenesis. 2016;37:777-786 pubmed publisher
    ..The K8-null mouse models also provide novel epithelial-derived robust colon-specific CRC models. ..
  15. Perriard G, Mathias A, Enz L, Canales M, Schluep M, Gentner M, et al. Interleukin-22 is increased in multiple sclerosis patients and targets astrocytes. J Neuroinflammation. 2015;12:119 pubmed publisher
  16. Dumoutier L, Lejeune D, Colau D, Renauld J. Cloning and characterization of IL-22 binding protein, a natural antagonist of IL-10-related T cell-derived inducible factor/IL-22. J Immunol. 2001;166:7090-5 pubmed
    ..We propose to name this natural cytokine antagonist IL-22BP for IL-22 binding protein. ..
  17. Kotenko S, Izotova L, Mirochnitchenko O, Esterova E, Dickensheets H, Donnelly R, et al. Identification, cloning, and characterization of a novel soluble receptor that binds IL-22 and neutralizes its activity. J Immunol. 2001;166:7096-103 pubmed
    ..Thus, the soluble receptor designated IL-22BP inhibits IL-22 activity by binding IL-22 and blocking its interaction with the cell surface IL-22R complex. ..
  18. Martin J, Bériou G, Heslan M, Bossard C, Jarry A, Abidi A, et al. IL-22BP is produced by eosinophils in human gut and blocks IL-22 protective actions during colitis. Mucosal Immunol. 2016;9:539-49 pubmed publisher
  19. Gruenberg B, Schoenemeyer A, Weiss B, Toschi L, Kunz S, Wolk K, et al. A novel, soluble homologue of the human IL-10 receptor with preferential expression in placenta. Genes Immun. 2001;2:329-34 pubmed
    ..The preferential expression of CRF2-s1 in placenta suggests a role for this receptor in establishing and maintaining successful pregnancy. ..
  20. de Moura P, Watanabe L, Bleicher L, Colau D, Dumoutier L, Lemaire M, et al. Crystal structure of a soluble decoy receptor IL-22BP bound to interleukin-22. FEBS Lett. 2009;583:1072-7 pubmed publisher
    ..Comparison of IL-22/IL-22BP and IL-22/IL-22R1 crystal structures shows that both receptors display an overlapping IL-22 binding surface, which is consistent with the inhibitory role played by IL-22 binding protein. ..
  21. Broquet A, Jacqueline C, Davieau M, Besbes A, Roquilly A, Martin J, et al. Interleukin-22 level is negatively correlated with neutrophil recruitment in the lungs in a Pseudomonas aeruginosa pneumonia model. Sci Rep. 2017;7:11010 pubmed publisher
    ..This study demonstrated that the IL-22/IL-22BP system plays a major role during Pseudomonas aeruginosa pneumonia by moderating neutrophil accumulation in the lungs that ultimately leads to epithelium protection. ..
  22. Xu W, Presnell S, Parrish Novak J, Kindsvogel W, Jaspers S, Chen Z, et al. A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist. Proc Natl Acad Sci U S A. 2001;98:9511-6 pubmed
    ..Because IL-22 induces the expression of acute phase reactants, IL-22RA2 may play an important role as an IL-22 antagonist in the regulation of inflammatory responses. ..
  23. Jinnohara T, Kanaya T, Hase K, Sakakibara S, Kato T, Tachibana N, et al. IL-22BP dictates characteristics of Peyer's patch follicle-associated epithelium for antigen uptake. J Exp Med. 2017;214:1607-1618 pubmed publisher
    ..As expected, FAE of IL-22BP-deficient (Il22ra2-/-) mice exhibited altered properties such as the enhanced expression of mucus and ..
  24. Badr A, Farag Y, Abdelshafy M, Riad N. Urinary interleukin 22 binding protein as a marker of lupus nephritis in Egyptian children with juvenile systemic lupus erythematosus. Clin Rheumatol. 2018;37:451-458 pubmed publisher
    ..Interleukin 22 (IL-22) is involved in tissue inflammation and is regulated by interleukin 22 binding protein (IL-22BP)...
  25. Wei C, Ho T, Liang W, Chen G, Chang M. Cloning and characterization of mouse IL-22 binding protein. Genes Immun. 2003;4:204-11 pubmed
    ..Treating B cells with mouse IL-22 induces production of reactive oxygen species, which mIL-22BP blocks. ..
  26. Kleinschmidt D, Giannou A, McGee H, Kempski J, Steglich B, Huber F, et al. A Protective Function of IL-22BP in Ischemia Reperfusion and Acetaminophen-Induced Liver Injury. J Immunol. 2017;199:4078-4090 pubmed publisher
    ..In conclusion, our data indicate that IL-22BP plays a protective role in acute liver damage, via controlling IL-22-induced Cxcl10 expression. ..
  27. Kingo K, Mossner R, Traks T, Rätsep R, Raud K, Reimann E, et al. Further association analysis of chr 6q22-24 suggests a role of IL-20RA polymorphisms in psoriasis. J Dermatol Sci. 2010;57:71-3 pubmed publisher
  28. Wang B, Zhao P, Zhou Y, Meng L, Zhu W, Jiang C, et al. Increased expression of Th17 cytokines and interleukin-22 correlates with disease activity in pristane-induced arthritis in rats. PLoS ONE. 2017;12:e0188199 pubmed publisher
  29. Weidenbusch M, Rodler S, Song S, Romoli S, Marschner J, Kraft F, et al. Gene expression profiling of the Notch-AhR-IL22 axis at homeostasis and in response to tissue injury. Biosci Rep. 2017;37: pubmed publisher
    ..PSEN1, basigin (BSG)/CD147, RBP-J, HES1, HES5, HEY1, HEYL, AHR, ARNT, ARNT2, CYP1A1, CYP24A1, IL-22, IL22RA1, IL22RA2, IL10RB, and STAT3 under homeostatic conditions in ten mature murine and human organs...
  30. Pan S, Yang D, Zhang J, Zhang Z, Zhang H, Liu X, et al. Temporal expression of interleukin-22, interleukin-22 receptor 1 and interleukin-22-binding protein during experimental periodontitis in rats. J Periodontal Res. 2017;: pubmed publisher
    ..The purpose of this study was to investigate histological changes and the levels of interleukin-22, interleukin-22 receptor 1 (IL-22R1) and interleukin-22-binding protein (IL-22BP) in experimental periodontitis...
  31. Lim C, Hong M, Savan R. Human IL-22 binding protein isoforms act as a rheostat for IL-22 signaling. Sci Signal. 2016;9:ra95 pubmed publisher
    ..Dysregulation of IL-22 signaling causes inflammatory diseases. IL-22 binding protein (IL-22BP; encoded by IL22RA2) is a soluble IL-22 receptor, which antagonizes IL-22 activity and has genetic associations with autoimmune ..
  32. Yang G, Yu J, Su J, Jiao L, Liu X, Zhu Y. Oral Administration of Lactobacillus rhamnosus GG Ameliorates Salmonella Infantis-Induced Inflammation in a Pig Model via Activation of the IL-22BP/IL-22/STAT3 Pathway. Front Cell Infect Microbiol. 2017;7:323 pubmed publisher
    ..Our results suggest that the mechanism by which LGG ameliorates the intestinal inflammation caused by S. Infantis involves the upregulation of T-bet, activation of STAT3, and downregulation of CCL20. ..
  33. Endam L, Bosse Y, Filali Mouhim A, Cormier C, Boisvert P, Boulet L, et al. Polymorphisms in the interleukin-22 receptor alpha-1 gene are associated with severe chronic rhinosinusitis. Otolaryngol Head Neck Surg. 2009;140:741-7 pubmed publisher
    ..Polymorphisms in IL22RA1 are associated with severe CRS. Replication and functional studies are involved to better understand the mechanism by which these polymorphisms contribute to the pathogenesis of CRS. ..
  34. Beyeen A, Adzemovic M, Ockinger J, Stridh P, Becanovic K, Laaksonen H, et al. IL-22RA2 associates with multiple sclerosis and macrophage effector mechanisms in experimental neuroinflammation. J Immunol. 2010;185:6883-90 pubmed publisher
    ..Through a combined approach including genetic and immunological investigation in an animal model and large-scale association studies of MS patients, we establish IL-22RA2 as an MS risk gene. ..
  35. Wu P, Li J, Kodangattil S, Luxenberg D, Bennett F, Martino M, et al. IL-22R, IL-10R2, and IL-22BP binding sites are topologically juxtaposed on adjacent and overlapping surfaces of IL-22. J Mol Biol. 2008;382:1168-83 pubmed publisher
    ..Our results also provide a model for how IL-19, IL-20, IL-24, and IL-26 which are other IL-10-like cytokines, interact with their respective cell surface receptors. ..
  36. Watanabe L, de Moura P, Nascimento A, Colau D, Dumoutier L, Renauld J, et al. Crystallization and preliminary X-ray diffraction analysis of human IL-22 bound to its soluble decoy receptor IL-22BP. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009;65:102-4 pubmed publisher
    ..75 A resolution. The crystal belonged to the tetragonal space group P4(1), with unit-cell parameters a = b = 67.9, c = 172.5 A, and contained two IL-22-IL-22BP complexes per asymmetric unit. ..
  37. Weiss B, Wolk K, Grünberg B, Volk H, Sterry W, Asadullah K, et al. Cloning of murine IL-22 receptor alpha 2 and comparison with its human counterpart. Genes Immun. 2004;5:330-6 pubmed
    ..Differential modulation of IL-22R alpha 2 mRNA expression was observed upon systemic inflammation in mice in spleen, thymus, and lymph node. ..
  38. Martin J, Wolk K, Beriou G, Abidi A, Witte Händel E, Louvet C, et al. Limited Presence of IL-22 Binding Protein, a Natural IL-22 Inhibitor, Strengthens Psoriatic Skin Inflammation. J Immunol. 2017;198:3671-3678 pubmed publisher
    ..we used imiquimod-induced skin disease in rodents and showed that rats with genetic IL-22BP deficiency (Il22ra2-/-) displayed exacerbated disease that associated with enhanced expression of IL-22-inducible ..
  39. de Vor I, van der Meulen P, Bekker V, Verhard E, Breuning M, Harnisch E, et al. Deletion of the entire interferon-γ receptor 1 gene causing complete deficiency in three related patients. J Clin Immunol. 2016;36:195-203 pubmed publisher
    ..IFNGR1 transcript was analyzed in RNA and the gene and adjacent regions were analyzed in DNA. Finally, IL22RA2 transcript levels were analyzed in whole blood cells and dendritic cells...