Abstract
Interleukin (IL)-22 is a member of the IL-10 family of cytokines and represents an important effector molecule of activated Th22, Th1, and Th17 cells, as well as Tc-cell subsets, γδ T cells, natural killer (NK), and NKT cells. IL-22 mediates its effects via a heterodimeric transmembrane receptor complex consisting of IL-22R1 and IL-10R2 and subsequent Janus kinase–signal transducers and activators of transcription (JAK–STAT) signaling pathways including Jak1, Tyk2, and STAT3. Whereas in some aspects, IL-22 acts synergistically with tumor necrosis factor-α, IL-1β, or IL-17, most functions of IL-22 are unique. Importantly, IL-22 does not serve the communication between immune cells. It mainly acts on epithelial cells and hepatocytes, where it favors the antimicrobial defense, regeneration, and protection against damage and induces acute phase reactants and some chemokines. This chapter illuminates in detail the properties of IL-22 with respect to its gene, protein structure, cellular sources, receptors, target cells, biological effects, and, finally, its role in chronic inflammatory diseases, tumors, and infection.
Similar content being viewed by others
References
Dumoutier L, Louahed J, Renauld JC (2000) Cloning and characterization of IL-10-related T cell-derived inducible factor (IL-TIF), a novel cytokine structurally related to IL-10 and inducible by IL-9. J Immunol 164:1814–1819
Moore KW, de Waal MR, Coffman RL, O’Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765
Schulze-Tanzil G, Zreiqat H, Sabat R, Kohl B, Halder A, Muller RD, John T (2009) Interleukin-10 and articular cartilage: experimental therapeutical approaches in cartilage disorders. Curr Gene Ther 9:306–315
Dumoutier L, Van Roost E, Colau D, Renauld JC (2000) Human interleukin-10-related T cell-derived inducible factor: molecular cloning and functional characterization as an hepatocyte-stimulating factor. Proc Natl Acad Sci U S A 97:10144–10149
Xie MH, Aggarwal S, Ho WH, Foster J, Zhang Z, Stinson J, Wood WI, Goddard AD, Gurney AL (2000) Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R. J Biol Chem 275:31335–31339
Blumberg H, Conklin D, Xu WF, Grossmann A, Brender T, Carollo S, Eagan M, Foster D, Haldeman BA, Hammond A, Haugen H, Jelinek L, Kelly JD, Madden K, Maurer MF, Parrish-Novak J, Prunkard D, Sexson S, Sprecher C, Waggie K, West J, Whitmore TE, Yao L, Kuechle MK, Dale BA, Chandrasekher YA (2001) Interleukin 20: discovery, receptor identification, and role in epidermal function. Cell 104:9–19
Gallagher G, Dickensheets H, Eskdale J, Izotova LS, Mirochnitchenko OV, Peat JD, Vazquez N, Pestka S, Donnelly RP, Kotenko SV (2000) Cloning, expression and initial characterization of interleukin-19 (IL-19), a novel homologue of human interleukin-10 (IL-10). Genes Immun 1:442–450
Jiang H, Su ZZ, Lin JJ, Goldstein NI, Young CS, Fisher PB (1996) The melanoma differentiation associated gene mda-7 suppresses cancer cell growth. Proc Natl Acad Sci U S A 93:9160–9165
Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen M, Shah NK, Langer JA, Sheikh F, Dickensheets H, Donnelly RP (2003) IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol 4:69–77
Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, Ostrander C, Dong D, Shin J, Presnell S, Fox B, Haldeman B, Cooper E, Taft D, Gilbert T, Grant FJ, Tackett M, Krivan W, McKnight G, Clegg C, Foster D, Klucher KM (2003) IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol 4:63–68
Sabat R, Wallace E, Endesfelder S, Wolk K (2007) IL-19 and IL-20: two novel cytokines with importance in inflammatory diseases. Expert Opin Ther Targets 11:601–612
Kotenko SV (2002) The family of IL-10-related cytokines and their receptors: related, but to what extent? Cytokine Growth Factor Rev 13:223–240
Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher PB (2004) Interleukin-10 and related cytokines and receptors. Annu Rev Immunol 22:929–979
Langer JA, Cutrone EC, Kotenko S (2004) The class II cytokine receptor (CRF2) family: overview and patterns of receptor–ligand interactions. Cytokine Growth Factor Rev 15:33–48
Wolk K, Sabat R (2006) Interleukin-22: a novel T- and NK-cell derived cytokine that regulates the biology of tissue cells. Cytokine Growth Factor Rev 17:367–380
Dumoutier L, Leemans C, Lejeune D, Kotenko SV, Renauld JC (2001) Cutting edge: STAT activation by IL-19, IL-20 and mda-7 through IL-20 receptor complexes of two types. J Immunol 167:3545–3549
Sheikh F, Baurin VV, Lewis-Antes A, Shah NK, Smirnov SV, Anantha S, Dickensheets H, Dumoutier L, Renauld JC, Zdanov A, Donnelly RP, Kotenko SV (2004) Cutting edge: IL-26 signals through a novel receptor complex composed of IL-20 receptor 1 and IL-10 receptor 2. J Immunol 172:2006–2010
Dumoutier L, Van Roost E, Ameye G, Michaux L, Renauld JC (2000) IL-TIF/IL-22: genomic organization and mapping of the human and mouse genes. Genes Immun 1:488–494
Nagem RA, Colau D, Dumoutier L, Renauld JC, Ogata C, Polikarpov I (2002) Crystal structure of recombinant human interleukin-22. Structure (Camb) 10:1051–1062
Xu T, Logsdon NJ, Walter MR (2005) Structure of insect-cell-derived IL-22. Acta Crystallogr D Biol Crystallogr 61:942–950
Logsdon NJ, Jones BC, Josephson K, Cook J, Walter MR (2002) Comparison of interleukin-22 and interleukin-10 soluble receptor complexes. J Interferon Cytokine Res 22:1099–1112
Logsdon NJ, Jones BC, Allman JC, Izotova L, Schwartz B, Pestka S, Walter MR (2004) The IL-10R2 binding hot spot on IL-22 is located on the N-terminal helix and is dependent on N-linked glycosylation. J Mol Biol 342:503–514
Wolk K, Kunz S, Asadullah K, Sabat R (2002) Cutting edge: immune cells as sources and targets of the IL-10 family members? J Immunol 168:5397–5402
Wolk K, Witte K, Witte E, Proesch S, Schulze-Tanzil G, Nasilowska K, Thilo J, Asadullah K, Sterry W, Volk HD, Sabat R (2008) Maturing dendritic cells are an important source of IL-29 and IL-20 that may cooperatively increase the innate immunity of keratinocytes. J Leukoc Biol 83:1181–1193
Wolk K, Witte E, Wallace E, Docke WD, Kunz S, Asadullah K, Volk HD, Sterry W, Sabat R (2006) IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur J Immunol 36:1309–1323
Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R (2004) IL-22 increases the innate immunity of tissues. Immunity 21:241–254
Duhen T, Geiger R, Jarrossay D, Lanzavecchia A, Sallusto F (2009) Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells. Nat Immunol 10:857–863
Trifari S, Kaplan CD, Tran EH, Crellin NK, Spits H (2009) 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. Nat Immunol 10:864–871
Volpe E, Servant N, Zollinger R, Bogiatzi SI, Hupe P, Barillot E, Soumelis V (2008) A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses. Nat Immunol 9:650–657
Acosta-Rodriguez EV, Rivino L, Geginat J, Jarrossay D, Gattorno M, Lanzavecchia A, Sallusto F, Napolitani G (2007) Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol 8:639–646
Zhou L, Chong MM, Littman DR (2009) Plasticity of CD4+ T cell lineage differentiation. Immunity 30:646–655
Veldhoen M, Hirota K, Westendorf AM, Buer J, Dumoutier L, Renauld JC, Stockinger B (2008) The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 453:106–109
Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1123–1132
Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q, Dong C (2005) A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 6:1133–1141
Chung Y, Yang X, Chang SH, Ma L, Tian Q, Dong C (2006) Expression and regulation of IL-22 in the IL-17-producing CD4+ T lymphocytes. Cell Res 16:902–907
Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M, Fouser LA (2006) Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 203:2271–2279
Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, Wu J, Ouyang W (2007) Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 445:648–651
Martin B, Hirota K, Cua DJ, Stockinger B, Veldhoen M (2009) Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals. Immunity 31:321–330
Siegemund S, Schutze N, Schulz S, Wolk K, Nasilowska K, Straubinger RK, Sabat R, Alber G (2009) Differential IL-23 requirement for IL-22 and IL-17A production during innate immunity against Salmonella enterica serovar Enteritidis. Int Immunol 21:555–565
Sutton CE, Lalor SJ, Sweeney CM, Brereton CF, Lavelle EC, Mills KH (2009) Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity. Immunity 31:331–341
Colonna M (2009) Interleukin-22-producing natural killer cells and lymphoid tissue inducer-like cells in mucosal immunity. Immunity 31:15–23
Goto M, Murakawa M, Kadoshima-Yamaoka K, Tanaka Y, Nagahira K, Fukuda Y, Nishimura T (2009) Murine NKT cells produce Th17 cytokine interleukin-22. Cell Immunol 254:81–84
Kotenko SV, Izotova LS, Mirochnitchenko OV, Esterova E, Dickensheets H, Donnelly RP, Pestka S (2001) Identification of the functional interleukin-22 (IL-22) receptor complex: the IL-10R2 chain (IL-10Rbeta ) is a common chain of both the IL-10 and IL-22 (IL-10-related T cell-derived inducible factor, IL-TIF) receptor complexes. J Biol Chem 276:2725–2732
Jones BC, Logsdon NJ, Walter MR (2008) Structure of IL-22 bound to its high-affinity IL-22R1 chain. Structure 16:1333–1344
Li J, Tomkinson KN, Tan XY, Wu P, Yan G, Spaulding V, Deng B, Annis-Freeman B, Heveron K, Zollner R, De Zutter G, Wright JF, Crawford TK, Liu W, Jacobs KA, Wolfman NM, Ling V, Pittman DD, Veldman GM, Fouser LA (2004) Temporal associations between interleukin 22 and the extracellular domains of IL-22R and IL-10R2. Int Immunopharmacol 4:693–708
Wolk K, Witte E, Reineke U, Witte K, Friedrich M, Sterry W, Asadullah K, Volk HD, Sabat R (2005) Is there an interaction between interleukin-10 and interleukin-22? Genes Immun 6:8–18
Reineke U, Schneider-Mergener J, Glaser RW, Stigler RD, Seifert M, Volk HD, Sabat R (1999) Evidence for conformationally different states of interleukin-10: binding of a neutralizing antibody enhances accessibility of a hidden epitope. J Mol Recognit 12:242–248
Bleicher L, de Moura PR, Watanabe L, Colau D, Dumoutier L, Renauld JC, Polikarpov I (2008) Crystal structure of the IL-22/IL-22R1 complex and its implications for the IL-22 signaling mechanism. FEBS Lett 582:2985–2992
Nagalakshmi ML, Rascle A, Zurawski S, Menon S, de Waal MR (2004) Interleukin-22 activates STAT3 and induces IL-10 by colon epithelial cells. Int Immunopharmacol 4:679–691
Boniface K, Bernard FX, Garcia M, Gurney AL, Lecron JC, Morel F (2005) IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes. J Immunol 174:3695–3702
Brand S, Beigel F, Olszak T, Zitzmann K, Eichhorst ST, Otte JM, Diepolder H, Marquardt A, Jagla W, Popp A, Leclair S, Herrmann K, Seiderer J, Ochsenkuhn T, Goke B, Auernhammer CJ, Dambacher J (2006) IL-22 is increased in active Crohn’s disease and promotes proinflammatory gene expression and intestinal epithelial cell migration. Am J Physiol Gastrointest Liver Physiol 290:G827–G838
Lejeune D, Dumoutier L, Constantinescu S, Kruijer W, Schuringa JJ, Renauld JC (2002) 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. J Biol Chem 277:33676–33682
Andoh A, Zhang Z, Inatomi O, Fujino S, Deguchi Y, Araki Y, Tsujikawa T, Kitoh K, Kim-Mitsuyama S, Takayanagi A, Shimizu N, Fujiyama Y (2005) Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts. Gastroenterology 129:969–984
Ikeuchi H, Kuroiwa T, Hiramatsu N, Kaneko Y, Hiromura K, Ueki K, Nojima Y (2005) Expression of interleukin-22 in rheumatoid arthritis: potential role as a proinflammatory cytokine. Arthritis Rheum 52:1037–1046
Dumoutier L, de Meester C, Tavernier J, Renauld JC (2009) A new activation modus of STAT3: a tyrosine-less region of the IL-22 receptor recruits STAT3 by interacting with its coiled-coil domain. J Biol Chem 284:26377–26384
Dumoutier L, Lejeune D, Colau D, Renauld JC (2001) Cloning and characterization of IL-22 binding protein, a natural antagonist of IL-10-related T cell-derived inducible factor/IL-22. J Immunol 166:7090–7095
Gruenberg BH, Schoenemeyer A, Weiss B, Toschi L, Kunz S, Wolk K, Asadullah K, Sabat R (2001) A novel, soluble homologue of the human IL-10 receptor with preferential expression in placenta. Genes Immun 2:329–334
Kotenko SV, Izotova LS, Mirochnitchenko OV, Esterova E, Dickensheets H, Donnelly RP, Pestka S (2001) Identification, cloning, and characterization of a novel soluble receptor that binds IL-22 and neutralizes its activity. J Immunol 166:7096–7103
Wei CC, Ho TW, Liang WG, Chen GY, Chang MS (2003) Cloning and characterization of mouse IL-22 binding protein. Genes Immun 4:204–211
Weiss B, Wolk K, Grunberg BH, Volk HD, Sterry W, Asadullah K, Sabat R (2004) Cloning of murine IL-22 receptor alpha 2 and comparison with its human counterpart. Genes Immun 5:330–336
Xu W, Presnell SR, Parrish-Novak J, Kindsvogel W, Jaspers S, Chen Z, Dillon SR, Gao Z, Gilbert T, Madden K, Schlutsmeyer S, Yao L, Whitmore TE, Chandrasekher Y, Grant FJ, Maurer M, Jelinek L, Storey H, Brender T, Hammond A, Topouzis S, Clegg CH, Foster DC (2001) A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist. Proc Natl Acad Sci U S A 98:9511–9516
Wolk K, Witte E, Hoffmann U, Doecke WD, Endesfelder S, Asadullah K, Sterry W, Volk HD, Wittig BM, Sabat R (2007) IL-22 induces lipopolysaccharide-binding protein in hepatocytes: a potential systemic role of IL-22 in Crohn’s disease. J Immunol 178:5973–5981
de Moura PR, Watanabe L, Bleicher L, Colau D, Dumoutier L, Lemaire MM, Renauld JC, Polikarpov I (2009) Crystal structure of a soluble decoy receptor IL-22BP bound to interleukin-22. FEBS Lett 583:1072–1077
Wu PW, Li J, Kodangattil SR, Luxenberg DP, Bennett F, Martino M, Collins M, Dunussi-Joannopoulos K, Gill DS, Wolfman NM, Fouser LA (2008) IL-22R, IL-10R2, and IL-22BP binding sites are topologically juxtaposed on adjacent and overlapping surfaces of IL-22. J Mol Biol 382:1168–1183
Aggarwal S, Xie MH, Maruoka M, Foster J, Gurney AL (2001) Acinar cells of the pancreas are a target of interleukin-22. J Interferon Cytokine Res 21:1047–1053
Parrish-Novak J, Xu W, Brender T, Yao L, Jones C, West J, Brandt C, Jelinek L, Madden K, McKernan PA, Foster DC, Jaspers S, Chandrasekher YA (2002) Interleukins 19, 20, and 24 signal through two distinct receptor complexes. Differences in receptor–ligand interactions mediate unique biological functions. J Biol Chem 277:47517–47523
Wolk K, Haugen HS, Xu W, Witte E, Waggie K, Anderson M, Vom Baur E, Witte K, Warszawska K, Philipp S, Johnson-Leger C, Volk HD, Sterry W, Sabat R (2009) IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-gamma are not. J Mol Med 87:523–536
Kunz S, Wolk K, Witte E, Witte K, Doecke WD, Volk HD, Sterry W, Asadullah K, Sabat R (2006) Interleukin (IL)-19, IL-20 and IL-24 are produced by and act on keratinocytes and are distinct from classical ILs. Exp Dermatol 15:991–1004
Sa SM, Valdez PA, Wu J, Jung K, Zhong F, Hall L, Kasman I, Winer J, Modrusan Z, Danilenko DM, Ouyang W (2007) The effects of IL-20 subfamily cytokines on reconstituted human epidermis suggest potential roles in cutaneous innate defense and pathogenic adaptive immunity in psoriasis. J Immunol 178:2229–2240
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 (2009) The Th17 cytokine IL-22 induces IL-20 production in keratinocytes: a novel immunological cascade with potential relevance in psoriasis. Eur J Immunol 39:3570–3581
Griffiths CE, Barker JN (2007) Pathogenesis and clinical features of psoriasis. Lancet 370:263–271
Sabat R, Philipp S, Hoflich C, Kreutzer S, Wallace E, Asadullah K, Volk HD, Sterry W, Wolk K (2007) Immunopathogenesis of psoriasis. Exp Dermatol 16:779–798
Schon MP, Boehncke WH (2005) Psoriasis. N Engl J Med 352:1899–1912
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 (2008) IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation. J Clin Invest 118:597–607
Endam LM, Bosse Y, Filali-Mouhim A, Cormier C, Boisvert P, Boulet LP, Hudson TJ, Desrosiers M (2009) Polymorphisms in the interleukin-22 receptor alpha-1 gene are associated with severe chronic rhinosinusitis. Otolaryngol Head Neck Surg 140:741–747
Li Z, Liu B, Maminishkis A, Mahesh SP, Yeh S, Lew J, Lim WK, Sen HN, Clarke G, Buggage R, Miller SS, Nussenblatt RB (2008) Gene expression profiling in autoimmune noninfectious uveitis disease. J Immunol 181:5147–5157
Zheng Y, Valdez PA, Danilenko DM, Hu Y, Sa SM, Gong Q, Abbas AR, Modrusan Z, Ghilardi N, de Sauvage FJ, Ouyang W (2008) Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med 14:282–289
Aujla SJ, Chan YR, Zheng M, Fei M, Askew DJ, Pociask DA, Reinhart TA, McAllister F, Edeal J, Gaus K, Husain S, Kreindler JL, Dubin PJ, Pilewski JM, Myerburg MM, Mason CA, Iwakura Y, Kolls JK (2008) IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat Med 14:275–281
Satoh-Takayama N, Vosshenrich CA, Lesjean-Pottier S, Sawa S, Lochner M, Rattis F, Mention JJ, Thiam K, Cerf-Bensussan N, Mandelboim O, Eberl G, Di Santo JP (2008) Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity 29:958–970
Liang SC, Long AJ, Bennett F, Whitters MJ, Karim R, Collins M, Goldman SJ, Dunussi-Joannopoulos K, Williams CM, Wright JF, Fouser LA (2007) An IL-17F/A heterodimer protein is produced by mouse Th17 cells and induces airway neutrophil recruitment. J Immunol 179:7791–7799
Schulz SM, Kohler G, Schutze N, Knauer J, Straubinger RK, Chackerian AA, Witte E, Wolk K, Sabat R, Iwakura Y, Holscher C, Muller U, Kastelein RA, Alber G (2008) Protective immunity to systemic infection with attenuated Salmonella enterica serovar Enteritidis in the absence of IL-12 is associated with IL-23-dependent IL-22, but not IL-17. J Immunol 181:7891–7901
Zenewicz LA, Yancopoulos GD, Valenzuela DM, Murphy AJ, Karow M, Flavell RA (2007) Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation. Immunity 27:647–659
Weber GF, Schlautkotter S, Kaiser-Moore S, Altmayr F, Holzmann B, Weighardt H (2007) Inhibition of interleukin-22 attenuates bacterial load and organ failure during acute polymicrobial sepsis. Infect Immun 75:1690–1697
Liu Y, Yang B, Zhou M, Li L, Zhou H, Zhang J, Chen H, Wu C (2009) Memory IL-22-producing CD4+ T cells specific for Candida albicans are present in humans. Eur J Immunol 39:1472–1479
Conti HR, Shen F, Nayyar N, Stocum E, Sun JN, Lindemann MJ, Ho AW, Hai JH, Yu JJ, Jung JW, Filler SG, Masso-Welch P, Edgerton M, Gaffen SL (2009) Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J Exp Med 206:299–311
Misse D, Yssel H, Trabattoni D, Oblet C, Lo Caputo S, Mazzotta F, Pene J, Gonzalez JP, Clerici M, Veas F (2007) IL-22 participates in an innate anti-HIV-1 host-resistance network through acute-phase protein induction. J Immunol 178:407–415
Levillayer F, Mas M, Levi-Acobas F, Brahic M, Bureau JF (2007) Interleukin 22 is a candidate gene for Tmevp3, a locus controlling Theiler’s virus-induced neurological diseases. Genetics 176:1835–1844
Dambacher J, Beigel F, Zitzmann K, Heeg MH, Goke B, Diepolder HM, Auernhammer CJ, Brand S (2008) The role of interleukin-22 in hepatitis C virus infection. Cytokine 41:209–216
Radaeva S, Sun R, Pan HN, Hong F, Gao B (2004) Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation. Hepatology 39:1332–1342
Sugimoto K, Ogawa A, Mizoguchi E, Shimomura Y, Andoh A, Bhan AK, Blumberg RS, Xavier RJ, Mizoguchi A (2008) IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. J Clin Invest 118:534–544
Zenewicz LA, Yancopoulos GD, Valenzuela DM, Murphy AJ, Stevens S, Flavell RA (2008) Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity 29:947–957
Kreymborg K, Etzensperger R, Dumoutier L, Haak S, Rebollo A, Buch T, Heppner FL, Renauld JC, Becher B (2007) IL-22 is expressed by Th17 cells in an IL-23-dependent fashion, but not required for the development of autoimmune encephalomyelitis. J Immunol 179:8098–8104
Chang H, Hanawa H, Liu H, Yoshida T, Hayashi M, Watanabe R, Abe S, Toba K, Yoshida K, Elnaggar R, Minagawa S, Okura Y, Kato K, Kodama M, Maruyama H, Miyazaki J, Aizawa Y (2006) Hydrodynamic-based delivery of an interleukin-22-Ig fusion gene ameliorates experimental autoimmune myocarditis in rats. J Immunol 177:3635–3643
Shen H, Goodall JC, Hill Gaston JS (2009) Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis Rheum 60:1647–1656
Geboes L, Dumoutier L, Kelchtermans H, Schurgers E, Mitera T, Renauld JC, Matthys P (2009) Proinflammatory role of the Th17 cytokine interleukin-22 in collagen-induced arthritis in C57BL/6 mice. Arthritis Rheum 60:390–395
Weber GF, Gaertner FC, Erl W, Janssen KP, Blechert B, Holzmann B, Weighardt H, Essler M (2006) 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. J Immunol 177:8266–8272
Ziesche E, Bachmann M, Kleinert H, Pfeilschifter J, Muhl H (2007) The interleukin-22/STAT3 pathway potentiates expression of inducible nitric-oxide synthase in human colon carcinoma cells. J Biol Chem 282:16006–16015
Bard JD, Gelebart P, Anand M, Amin HM, Lai R (2008) Aberrant expression of IL-22 receptor 1 and autocrine IL-22 stimulation contribute to tumorigenicity in ALK+ anaplastic large cell lymphoma. Leukemia 22:1595–1603
Zhang W, Chen Y, Wei H, Zheng C, Sun R, Zhang J, Tian Z (2008) Antiapoptotic activity of autocrine interleukin-22 and therapeutic effects of interleukin-22-small interfering RNA on human lung cancer xenografts. Clin Cancer Res 14:6432–6439
Haider AS, Lowes MA, Suarez-Farinas M, Zaba LC, Cardinale I, Khatcherian A, Novitskaya I, Wittkowski KM, Krueger JG (2008) Identification of cellular pathways of “type 1,” Th17 T cells, and TNF- and inducible nitric oxide synthase-producing dendritic cells in autoimmune inflammation through pharmacogenomic study of cyclosporine A in psoriasis. J Immunol 180:1913–1920
Boniface K, Guignouard E, Pedretti N, Garcia M, Delwail A, Bernard FX, Nau F, Guillet G, Dagregorio G, Yssel H, Lecron JC, Morel F (2007) A role for T cell-derived interleukin 22 in psoriatic skin inflammation. Clin Exp Immunol 150:407–415
Guttman-Yassky E, Lowes MA, Fuentes-Duculan J, Zaba LC, Cardinale I, Nograles KE, Khatcherian A, Novitskaya I, Carucci JA, Bergman R, Krueger JG (2008) Low expression of the IL-23/Th17 pathway in atopic dermatitis compared to psoriasis. J Immunol 181:7420–7427
Pene J, Chevalier S, Preisser L, Venereau E, Guilleux MH, Ghannam S, Moles JP, Danger Y, Ravon E, Lesaux S, Yssel H, Gascan H (2008) Chronically inflamed human tissues are infiltrated by highly differentiated th17 lymphocytes. J Immunol 180:7423–7430
Philipp S, Wolk K, Kreutzer S, Wallace E, Ludwig N, Roewert J, Hoflich C, Volk HD, Sterry W, Sabat R (2006) The evaluation of psoriasis therapy with biologics leads to a revision of the current view of the pathogenesis of this disorder. Expert Opin Ther Targets 10:817–831
Sabat R, Sterry W, Philipp S, Wolk K (2007) Three decades of psoriasis research: where has it led us? Clin Dermatol 25:504–509
Cargill M, Schrodi SJ, Chang M, Garcia VE, Brandon R, Callis KP, Matsunami N, Ardlie KG, Civello D, Catanese JJ, Leong DU, Panko JM, McAllister LB, Hansen CB, Papenfuss J, Prescott SM, White TJ, Leppert MF, Krueger GG, Begovich AB (2007) A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet 80:273–290
Garcia VE, Chang M, Brandon R, Li Y, Matsunami N, Callis-Duffin KP, Civello D, Rowland CM, Bui N, Catanese JJ, Krueger GG, Leppert MF, Begovich AB, Schrodi SJ (2008) Detailed genetic characterization of the interleukin-23 receptor in psoriasis. Genes Immun 9:546–555
Weger W, Hofer A, Wolf P, El-Shabrawi Y, Renner W, Kerl H, Salmhofer W (2009) Common polymorphisms in the interleukin-22 gene are not associated with chronic plaque psoriasis. Exp Dermatol 18:796–798
Leppkes M, Becker C, Ivanov II, Hirth S, Wirtz S, Neufert C, Pouly S, Murphy AJ, Valenzuela DM, Yancopoulos GD, Becher B, Littman DR, Neurath MF (2009) RORgamma-expressing Th17 cells induce murine chronic intestinal inflammation via redundant effects of IL-17A and IL-17F. Gastroenterology 136:257–267
Acknowledgments
We thank the German Ministry of Education and Research (Bundesministerium für Bildung und Forschung) for generous support.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wolk, K., Witte, E., Witte, K. et al. Biology of interleukin-22. Semin Immunopathol 32, 17–31 (2010). https://doi.org/10.1007/s00281-009-0188-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00281-009-0188-x