Skip to main content

Advertisement

SpringerLink
Log in

Role of IL-22 in intestinal microenvironment and potential targeted therapy through diet

  • Review
  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

IL-22 is a type 2 receptor cytokine in IL-10 family. IL-22 is usually secreted by innate and adaptive immune cells and takes its effects on non-hematopoietic cells. Through activate STAT3 pathway, IL-22 plays an important role in infection clearance and tissue regeneration, which is critical for barrier integrate and homeostasis. Abnormal activation of IL-22 signal was observed in inflammation diseases, autoimmune diseases, and cancers. We review the recent discoveries about the mechanism and regulation of IL-22 signal pathway from the perspective of intestinal micro-environment. Diet-based IL-22 target therapeutic strategies and their potential clinical significance will also be discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Dumoutier L, Louahed J, Renauld JC. 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. 2000;164(4):1814–9.

    Article  CAS  PubMed  Google Scholar 

  2. Xie MH, Aggarwal S, Ho WH, Foster J, Zhang Z, Stinson J, et al. Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R. J Biol Chem. 2000;275(40):31335–9.

    Article  CAS  PubMed  Google Scholar 

  3. Ikeuchi H, Kuroiwa T, Hiramatsu N, Kaneko Y, Hiromura K, Ueki K, et al. Expression of interleukin-22 in rheumatoid arthritis: potential role as a proinflammatory cytokine. Arthritis Rheum. 2005;52(4):1037–46.

    Article  CAS  PubMed  Google Scholar 

  4. Lejeune D, Dumoutier L, Constantinescu S, Kruijer W, Schuringa JJ, Renauld JC. 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. 2002;277(37):33676–82.

    Article  CAS  PubMed  Google Scholar 

  5. Andoh A, Zhang Z, Inatomi O, Fujino S, Deguchi Y, Araki Y, et al. Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts. Gastroenterology. 2005;129(3):969–84.

    Article  CAS  PubMed  Google Scholar 

  6. Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R. IL-22 increases the innate immunity of tissues. Immunity. 2004;21(2):241–54.

    Article  CAS  PubMed  Google Scholar 

  7. Brand S, Dambacher J, Beigel F, Zitzmann K, Heeg MH, Weiss TS, et al. IL-22-mediated liver cell regeneration is abrogated by SOCS-1/3 overexpression in vitro. Am J Physiol Gastrointest Liver Physiol. 2007;292(4):G1019–28.

    Article  CAS  PubMed  Google Scholar 

  8. Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M, et al. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med. 2006;203(10):2271–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Aujla SJ, Chan YR, Zheng M, Fei M, Askew DJ, Pociask DA, et al. IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat Med. 2008;14(3):275–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sugimoto K, Ogawa A, Mizoguchi E, Shimomura Y, Andoh A, Bhan AK, et al. IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. J Clin Invest. 2008;118(2):534–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Weidenbusch M, Song S, Iwakura T, Shi C, Rodler S, Kobold S, et al. IL-22 sustains epithelial integrity in progressive kidney remodeling and fibrosis. Physiol Rep. 2018;6(16):e13817.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Aggarwal S, Xie MH, Maruoka M, Foster J, Gurney AL. Acinar cells of the pancreas are a target of interleukin-22. J Interferon Cytokine Res: Off J Int Soc Interferon Cytokine Res. 2001;21(12):1047–53.

    Article  CAS  Google Scholar 

  13. Gurney AL. IL-22, a Th1 cytokine that targets the pancreas and select other peripheral tissues. Int Immunopharmacol. 2004;4(5):669–77.

    Article  CAS  PubMed  Google Scholar 

  14. Chung Y, Yang X, Chang SH, Ma L, Tian Q, Dong C. Expression and regulation of IL-22 in the IL-17-producing CD4+ T lymphocytes. Cell Res. 2006;16(11):902–7.

    Article  CAS  PubMed  Google Scholar 

  15. Trifari S, Kaplan CD, Tran EH, Crellin NK, Spits H. 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. 2009;10(8):864–71.

    Article  CAS  PubMed  Google Scholar 

  16. Zheng Y, Valdez PA, Danilenko DM, Hu Y, Sa SM, Gong Q, et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med. 2008;14(3):282–9.

    Article  CAS  PubMed  Google Scholar 

  17. Wolk K, Kunz S, Asadullah K, Sabat R. Cutting edge: immune cells as sources and targets of the IL-10 family members? J Immunol. 2002;168(11):5397–402.

    Article  CAS  PubMed  Google Scholar 

  18. Satoh-Takayama N, Vosshenrich CA, Lesjean-Pottier S, Sawa S, Lochner M, Rattis F, et al. Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity. 2008;29(6):958–70.

    Article  CAS  PubMed  Google Scholar 

  19. Lee Y, Kumagai Y, Jang MS, Kim JH, Yang BG, Lee EJ, et al. Intestinal Lin- c-Kit+ NKp46- CD4- population strongly produces IL-22 upon IL-1beta stimulation. J Immunol. 2013;190(10):5296–305.

    Article  CAS  PubMed  Google Scholar 

  20. Tripathi D, Radhakrishnan RK, SivangalaThandi R, Paidipally P, Devalraju KP, Neela VSK, et al. IL-22 produced by type 3 innate lymphoid cells (ILC3s) reduces the mortality of type 2 diabetes mellitus (T2DM) mice infected with Mycobacterium tuberculosis. PLoS Pathog. 2019;15(12):e1008140.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Cobb LM, Verneris MR. Therapeutic manipulation of innate lymphoid cells. JCI Insight. 2021;6(6):e146006.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Li YY, Wang XJ, Su YL, Wang Q, Huang SW, Pan ZF, et al. Baicalein ameliorates ulcerative colitis by improving intestinal epithelial barrier via AhR/IL-22 pathway in ILC3s. Acta Pharmacol Sin. 2022;43(6):1495–507.

    Article  CAS  PubMed  Google Scholar 

  23. Becker C, Wirtz S, Blessing M, Pirhonen J, Strand D, Bechthold O, et al. Constitutive p40 promoter activation and IL-23 production in the terminal ileum mediated by dendritic cells. J Clin Investig. 2003;112(5):693–706.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Longman RS, Diehl GE, Victorio DA, Huh JR, Galan C, Miraldi ER, et al. CX(3)CR1(+) mononuclear phagocytes support colitis-associated innate lymphoid cell production of IL-22. J Exp Med. 2014;211(8):1571–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kamada N, Hisamatsu T, Okamoto S, Chinen H, Kobayashi T, Sato T, et al. Unique CD14 intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-gamma axis. J Clin Investig. 2008;118(6):2269–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Dumoutier L, Lejeune D, Colau D, Renauld JC. 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(12):7090–5.

    Article  CAS  PubMed  Google Scholar 

  27. Jones SA, Horiuchi S, Topley N, Yamamoto N, Fuller GM. The soluble interleukin 6 receptor: mechanisms of production and implications in disease. FASEB J: Off Publ Fed Am Soc Exp Biol. 2001;15(1):43–58.

    Article  CAS  Google Scholar 

  28. Xu W, Presnell SR, 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(17):9511–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Martin JC, Beriou G, Heslan M, Chauvin C, Utriainen L, Aumeunier A, et al. Interleukin-22 binding protein (IL-22BP) is constitutively expressed by a subset of conventional dendritic cells and is strongly induced by retinoic acid. Mucosal Immunol. 2014;7(1):101–13.

    Article  CAS  PubMed  Google Scholar 

  30. Huber S, Gagliani N, Zenewicz LA, Huber FJ, Bosurgi L, Hu B, et al. IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine. Nature. 2012;491(7423):259–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Martin JC, Beriou 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(2):539–49.

    Article  CAS  PubMed  Google Scholar 

  32. Zenewicz LA. IL-22: There is a gap in our knowledge. Immunohorizons. 2018;2(6):198–207.

    Article  CAS  PubMed  Google Scholar 

  33. Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R. IL-22 Increases the Innate Immunity of Tissues. Immunity. 2004;21(2):241–54.

    Article  CAS  PubMed  Google Scholar 

  34. Starkey MR, Plank MW, Casolari P, Papi A, Pavlidis S, Guo Y, et al. IL-22 and its receptors are increased in human and experimental COPD and contribute to pathogenesis. Eur Respir J. 2019;54(1):1800174.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wang Y, Zhou Q, Chen L, Dong L, Xiong M, Xie X, et al. Identification of genetic variants of the IL-22 gene in association with an altered risk of COPD susceptibility. Clin Respir J. 2022;16(8):537–45

  36. Tachiiri A, Imamura R, Wang Y, Fukui M, Umemura M, Suda T. Genomic structure and inducible expression of the IL-22 receptor alpha chain in mice. Genes Immun. 2003;4(2):153–9.

    Article  CAS  PubMed  Google Scholar 

  37. Stoy S, Laursen TL, Glavind E, Eriksen PL, Terczynska-Dyla E, Magnusson NE, et al. Low interleukin-22 binding protein is associated with high mortality in alcoholic hepatitis and modulates interleukin-22 receptor expression. Clin Transl Gastroenterol. 2020;11(8):e00197.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Keir M, Yi Y, Lu T, Ghilardi N. The role of IL-22 in intestinal health and disease. J Exp Med. 2020;217(3):e20192195.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Cella M, Fuchs A, Vermi W, Facchetti F, Otero K, Lennerz JK, et al. A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature. 2009;457(7230):722–5.

    Article  CAS  PubMed  Google Scholar 

  40. Yang FC, Chiu PY, Chen Y, Mak TW, Chen NJ. TREM-1-dependent M1 macrophage polarization restores intestinal epithelium damaged by DSS-induced colitis by activating IL-22-producing innate lymphoid cells. J Biomed Sci. 2019;26(1):46.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Hebert KD, McLaughlin N, Galeas-Pena M, Zhang Z, Eddens T, Govero A, et al. Targeting the IL-22/IL-22BP axis enhances tight junctions and reduces inflammation during influenza infection. Mucosal Immunol. 2020;13(1):64–74.

    Article  CAS  PubMed  Google Scholar 

  42. Dalmas E, Venteclef N, Caer C, Poitou C, Cremer I, Aron-Wisnewsky J, et al. T cell-derived IL-22 amplifies IL-1beta-driven inflammation in human adipose tissue: relevance to obesity and type 2 diabetes. Diabetes. 2014;63(6):1966–77.

    Article  CAS  PubMed  Google Scholar 

  43. Boniface K, Guignouard E, Pedretti N, Garcia M, Delwail A, Bernard FX, et al. A role for T cell-derived interleukin 22 in psoriatic skin inflammation. Clin Exp Immunol. 2007;150(3):407–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Zenewicz LA, Yancopoulos GD, Valenzuela DM, Murphy AJ, Stevens S, Flavell RA. Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity. 2008;29(6):947–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Grizotte-Lake M, Zhong G, Duncan K, Kirkwood J, Iyer N, Smolenski I, et al. Commensals suppress intestinal epithelial cell retinoic acid synthesis to regulate interleukin-22 activity and prevent microbial dysbiosis. Immunity. 2018;49(6):1103-15 e6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Behnsen J, Jellbauer S, Wong CP, Edwards RA, George MD, Ouyang W, et al. The cytokine IL-22 promotes pathogen colonization by suppressing related commensal bacteria. Immunity. 2014;40(2):262–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Santos AJM, Lo YH, Mah AT, Kuo CJ. The intestinal stem cell niche: homeostasis and adaptations. Trends Cell Biol. 2018;28(12):1062–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Ratanasirintrawoot S, Israsena N. Stem cells in the intestine: possible roles in pathogenesis of irritable bowel syndrome. J Neurogastroenterol Motil. 2016;22(3):367–82.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Aparicio-Domingo P, Romera-Hernandez M, Karrich JJ, Cornelissen F, Papazian N, Lindenbergh-Kortleve DJ, et al. Type 3 innate lymphoid cells maintain intestinal epithelial stem cells after tissue damage. J Exp Med. 2015;212(11):1783–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Glal D, Sudhakar JN, Lu HH, Liu MC, Chiang HY, Liu YC, et al. ATF3 sustains IL-22-induced STAT3 phosphorylation to maintain mucosal immunity through inhibiting phosphatases. Front Immunol. 2018;9:2522.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Lindemans CA, Calafiore M, Mertelsmann AM, O’Connor MH, Dudakov JA, Jenq RR, et al. Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration. Nature. 2015;528(7583):560–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Gronke K, Diefenbach A. Regenerative biology: innate immunity repairs gut lining. Nature. 2015;528(7583):488–9.

    Article  CAS  PubMed  Google Scholar 

  53. Ray K. Stem cells: IL-22 activates ISCs for intestinal regeneration. Nat Rev Gastroenterol Hepatol. 2016;13(2):64.

    Article  PubMed  Google Scholar 

  54. Hanash AM, Dudakov JA, Hua G, O’Connor MH, Young LF, Singer NV, et al. Interleukin-22 protects intestinal stem cells from immune-mediated tissue damage and regulates sensitivity to graft versus host disease. Immunity. 2012;37(2):339–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Zha JM, Li HS, Lin Q, Kuo WT, Jiang ZH, Tsai PY, et al. Interleukin 22 Expands Transit-Amplifying Cells While Depleting Lgr5(+) Stem cells via inhibition of Wnt and notch signaling. Cell Mol Gastroenterol Hepatol. 2019;7(2):255–74.

    Article  PubMed  Google Scholar 

  56. Zwarycz B, Gracz AD, Rivera KR, Williamson IA, Samsa LA, Starmer J, et al. IL22 Inhibits epithelial stem cell expansion in an ileal organoid model. Cell Mol Gastroenterol Hepatol. 2019;7(1):1–17.

    Article  PubMed  Google Scholar 

  57. Abo H, Denning TL. Epithelial traffic control: IL22 gives TA cells the green light. Cell Mol Gastroenterol Hepatol. 2019;7(2):409–10.

    Article  PubMed  Google Scholar 

  58. Brand S, Beigel F, Olszak T, Zitzmann K, Eichhorst ST, Otte JM, et al. 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. 2006;290(4):G827–38.

    Article  CAS  PubMed  Google Scholar 

  59. Soontararak S, Chow L, Johnson V, Coy J, Wheat W, Regan D, et al. Mesenchymal stem cells (MSC) derived from induced pluripotent stem cells (iPSC) equivalent to adipose-derived MSC in promoting intestinal healing and microbiome normalization in mouse inflammatory bowel disease model. Stem Cells Transl Med. 2018;7(6):456–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. El-Zayadi AA, Jones EA, Churchman SM, Baboolal TG, Cuthbert RJ, El-Jawhari JJ, et al. Interleukin-22 drives the proliferation, migration and osteogenic differentiation of mesenchymal stem cells: a novel cytokine that could contribute to new bone formation in spondyloarthropathies. Rheumatology. 2017;56(3):488–93.

    CAS  PubMed  Google Scholar 

  61. Kryczek I, Lin Y, Nagarsheth N, Peng D, Zhao L, Zhao E, et al. IL-22(+)CD4(+) T cells promote colorectal cancer stemness via STAT3 transcription factor activation and induction of the methyltransferase DOT1L. Immunity. 2014;40(5):772–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Bergmann H, Roth S, Pechloff K, Kiss EA, Kuhn S, Heikenwalder M, et al. Card9-dependent IL-1beta regulates IL-22 production from group 3 innate lymphoid cells and promotes colitis-associated cancer. Eur J Immunol. 2017;47(8):1342–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Gronke K, Hernandez PP, Zimmermann J, Klose CSN, Kofoed-Branzk M, Guendel F, et al. Interleukin-22 protects intestinal stem cells against genotoxic stress. Nature. 2019;566(7743):249–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Jin Y, Meng L, Yang H, Cheng S, Xiao Y, Wang X, et al. The IL-22 gene rs2227478 polymorphism significantly decreases the risk of colorectal cancer in a Han Chinese population. Pathol Res Pract. 2021;228:153690.

    Article  CAS  PubMed  Google Scholar 

  65. Mohebbi SR, Karimi K, Rostami F, Kazemian S, Azimzadeh P, Mirtalebi H, et al. Association of IL-22 and IL-22RA1 gene variants in Iranian patients with colorectal cancer. Gastroenterol Hepatol Bed Bench. 2021;14(Suppl1):S58–65.

    PubMed  PubMed Central  Google Scholar 

  66. Guillon A, Gueugnon F, Mavridis K, Dalloneau E, Jouan Y, Diot P, et al. Interleukin-22 receptor is overexpressed in nonsmall cell lung cancer and portends a poor prognosis. Eur Respir J. 2016;47(4):1277–80.

    Article  CAS  PubMed  Google Scholar 

  67. Wu Y, Min J, Ge C, Shu J, Tian D, Yuan Y, et al. Interleukin 22 in liver injury, inflammation and cancer. Int J Biol Sci. 2020;16(13):2405–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Wang T, Zhang Z, Xing H, Wang L, Zhang G, Yu N, et al. Elevated Th22 cells and related cytokines in patients with epithelial ovarian cancer. Medicine (Baltimore). 2017;96(43):e8359.

    Article  CAS  PubMed  Google Scholar 

  69. Akil H, Abbaci A, Lalloue F, Bessette B, Costes LM, Domballe L, et al. IL22/IL-22R pathway induces cell survival in human glioblastoma cells. PLoS ONE. 2015;10(3):e0119872.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Zhuang Y, Peng LS, Zhao YL, Shi Y, Mao XH, Guo G, et al. Increased intratumoral IL-22-producing CD4(+) T cells and Th22 cells correlate with gastric cancer progression and predict poor patient survival. Cancer Immunol Immunother: CII. 2012;61(11):1965–75.

    Article  CAS  PubMed  Google Scholar 

  71. Fukui H, Zhang X, Sun C, Hara K, Kikuchi S, Yamasaki T, et al. IL-22 produced by cancer-associated fibroblasts promotes gastric cancer cell invasion via STAT3 and ERK signaling. Br J Cancer. 2014;111(4):763–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Wu T, Cui L, Liang Z, Liu C, Liu Y, Li J. Elevated serum IL-22 levels correlate with chemoresistant condition of colorectal cancer. Clin Immunol. 2013;147(1):38–9.

    Article  CAS  PubMed  Google Scholar 

  73. Qin SY, Yang XW, Luo W, Chen M, Liu ZL, Su SB, et al. Association of interleukin 22 polymorphisms with gastric cancer risk. Tumour Biol: J Int Soc Oncodev Biol Med. 2015;36(3):2033–9.

    Article  CAS  Google Scholar 

  74. Huang YH, Cao YF, Jiang ZY, Zhang S, Gao F. Th22 cell accumulation is associated with colorectal cancer development. World J Gastroenterol: WJG. 2015;21(14):4216–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Sun D, Lin Y, Hong J, Chen H, Nagarsheth N, Peng D, et al. Th22 cells control colon tumorigenesis through STAT3 and polycomb repression complex 2 signaling. Oncoimmunology. 2016;5(8):e1082704.

    Article  PubMed  Google Scholar 

  76. Veldhoen M, Hirota K, Westendorf AM, Buer J, Dumoutier L, Renauld JC, et al. The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature. 2008;453(7191):106–9.

    Article  CAS  PubMed  Google Scholar 

  77. Perez LG, Kempski J, McGee HM, Pelzcar P, Agalioti T, Giannou A, et al. TGF-beta signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer. Nat Commun. 2020;11(1):2608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Qiu J, Heller JJ, Guo X, Chen ZM, Fish K, Fu YX, et al. The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells. Immunity. 2012;36(1):92–104.

    Article  CAS  PubMed  Google Scholar 

  79. Tian Z, van Velkinburgh JC, Wu Y, Ni B. Innate lymphoid cells involve in tumorigenesis. Int J Cancer J Int du Cancer. 2016;138(1):22–9.

    Article  CAS  Google Scholar 

  80. Lamas B, Richard ML, Leducq V, Pham HP, Michel ML, Da Costa G, et al. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat Med. 2016;22(6):598–605.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Jiang R, Wang H, Deng L, Hou J, Shi R, Yao M, et al. IL-22 is related to development of human colon cancer by activation of STAT3. BMC Cancer. 2013;13:59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Ji Y, Yang X, Li J, Lu Z, Li X, Yu J, et al. IL-22 promotes the migration and invasion of gastric cancer cells via IL-22R1/AKT/MMP-9 signaling. Int J Clin Exp Pathol. 2014;7(7):3694–703.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Ki SH, Park O, Zheng M, Morales-Ibanez O, Kolls JK, Bataller R, et al. Interleukin-22 treatment ameliorates alcoholic liver injury in a murine model of chronic-binge ethanol feeding: role of signal transducer and activator of transcription 3. Hepatology. 2010;52(4):1291–300.

    Article  CAS  PubMed  Google Scholar 

  84. Hamade DF, Espinal A, Yu J, Leibowitz BJ, Fisher R, Hou W, et al. Lactobacillus reuteri releasing IL-22 (LR-IL-22) facilitates intestinal radioprotection for whole-abdomen irradiation (WAI) of ovarian cancer. Radiat Res. 2022;198(1):89–105.

    Article  CAS  PubMed  Google Scholar 

  85. Zou J, Chassaing B, Singh V, Pellizzon M, Ricci M, Fythe MD, et al. Fiber-mediated nourishment of gut microbiota protects against diet-induced obesity by restoring IL-22-mediated colonic health. Cell Host & Microbe. 2018;23(1):41-53 e4.

    Article  CAS  Google Scholar 

  86. Torquati L, Coombes JS, Murray L, Hasnain SZ, Mallard AR, McGuckin MA, et al. Fibre intake is independently associated with increased circulating interleukin-22 in individuals with metabolic syndrome. Nutrients. 2019;11(4):815.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Huo Y, Liu Z, Xuan H, Lu C, Yu L, Bao W, et al. Effects of bamboo vinegar powder on growth performance and mRNA expression levels of interleukin-10, interleukin-22, and interleukin-25 in immune organs of weaned piglets. Anim Nutr. 2016;2(2):111–8.

    Article  PubMed  PubMed Central  Google Scholar 

  88. 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;103:1217–23.

    Article  CAS  PubMed  Google Scholar 

  89. Monteleone I, Rizzo A, Sarra M, Sica G, Sileri P, Biancone L, et al. Aryl hydrocarbon receptor-induced signals up-regulate IL-22 production and inhibit inflammation in the gastrointestinal tract. Gastroenterology. 2011;141(1):237–48 (48 e1).

    Article  CAS  PubMed  Google Scholar 

  90. Barros KV, FlorSilveira VL, Laranjeira MS, Wandalsen NF, Passeti S, de Oliveira R, et al. Evidence for involvement of IL-9 and IL-22 in cows’ milk allergy in infants. Nutrients. 2017;9(10):1048.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Sabat R, Ouyang W, Wolk K. Therapeutic opportunities of the IL-22-IL-22R1 system. Nat Rev Drug Discovery. 2014;13(1):21–38.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This project was supported by grants from National Key Research and Development Program of China (2021YFF1200800) and Natural Science Foundation of Tianjin (21JCZDJC00430).

Author information

Authors and Affiliations

  1. Institute of Medical Engineering & Translational Medicine, Tianjin University, 92 Weijin Road, Tianjin, 300072, China

    Peiying Wang & Youwei Wang

  2. Department of Internal Medicine, Division of Hematology, The Ohio State University, 400 W. 12th Ave, Columbus, OH, 43210, USA

    Wing Keung Chan

  3. Tianjin Economic-Technological Development Area (TEDA) Hospital, 65 3rd Ave, Tianjin, 300451, China

    Jiming Wang

  4. Department of Critical Care Medicine, Zhejiang Hospital, 1229 Gudun Road, Hangzhou, 310030, China

    Zhouxin Yang

Authors
  1. Peiying Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wing Keung Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jiming Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhouxin Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Youwei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Zhouxin Yang or Youwei Wang.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Summary

This paper reviews the mechanism and regulation of IL-22 signaling pathway in intestinal microenvironment and discusses the diet based on IL-22 targeted therapy strategy.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, P., Chan, W.K., Wang, J. et al. Role of IL-22 in intestinal microenvironment and potential targeted therapy through diet. Immunol Res 71, 121–129 (2023). https://doi.org/10.1007/s12026-022-09325-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-022-09325-5

Keywords

Search

Navigation