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Is there an interaction between interleukin-10 and interleukin-22?

Genes & Immunity volume 6, pages 8–18 (2005)Cite this article

Abstract

Interleukin(IL)-10 and IL-22 are structurally related cytokines. Their heterodimeric receptors consist of the cytokine-specific chains IL-10R1 and IL-22R1, respectively, and the common chain IL-10R2. This study focused on the question of whether IL-10 modulates IL-22 effects and vice versa. This question is important because IL-10 and IL-22 exert anti- and proinflammatory effects, respectively, and, as we show here, are simultaneously present in both systemic and local inflammation. The revealed lacking concomitance of IL-10R1 and IL-22R1 on identical cells excluded any possible interaction between IL-10 and IL-22 apart from the competition for IL-10R2. To study this competition, monocytes and hepatocytes were chosen. The dependence of the cytokine action on IL-10R2 was verified. Interestingly, no influence of IL-22 on IL-10 effects was observed. The same was true when IL-22 was used in complex with IL-22-binding protein. Similarly, no influence of IL-10 was found on IL-22 action. This missing competition seemed to be due to a lack of binding between IL-10R2 and the native cytokines in the absence of their corresponding R1 chain. However, IL-10R2 interacted with defined IL-10- and IL-22-derived peptides supporting the hypothesis that cytokine binding to its corresponding R1 chain creates a binding site on this cytokine for IL-10R2.

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References

  1. Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A . Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001; 19: 683–765.

    Article  CAS  PubMed  Google Scholar 

  2. Fiorentino DF, Bond MW, Mosmann TR . Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med 1989; 170: 2081–2095.

    Article  CAS  PubMed  Google Scholar 

  3. de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE . Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 1991; 174: 1209–1220.

    Article  CAS  PubMed  Google Scholar 

  4. Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O’Garra A . IL-10 inhibits cytokine production by activated macrophages. J Immunol 1991; 147: 3815–3822.

    CAS  PubMed  Google Scholar 

  5. de Waal Malefyt R, Haanen J, Spits H et al. Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med 1991; 174: 915–924.

    Article  CAS  PubMed  Google Scholar 

  6. Willems F, Marchant A, Delville JP et al. Interleukin-10 inhibits B7 and intercellular adhesion molecule-1 expression on human monocytes. Eur J Immunol 1994; 24: 1007–1009.

    Article  CAS  PubMed  Google Scholar 

  7. Berkman N, John M, Roesems G, Jose PJ, Barnes PJ, Chung KF . Inhibition of macrophage inflammatory protein-1 alpha expression by IL-10. Differential sensitivities in human blood monocytes and alveolar macrophages. J Immunol 1995; 155: 4412–4418.

    CAS  PubMed  Google Scholar 

  8. Marfaing-Koka A, Maravic M, Humbert M, Galanaud P, Emilie D . Contrasting effects of IL-4, IL-10 and corticosteroids on RANTES production by human monocytes. Int Immunol 1996; 8: 1587–1594.

    Article  CAS  PubMed  Google Scholar 

  9. Kopydlowski KM, Salkowski CA, Cody MJ et al. Regulation of macrophage chemokine expression by lipopolysaccharide in vitro and in vivo. J Immunol 1999; 163: 1537–1544.

    CAS  PubMed  Google Scholar 

  10. te Velde AA, de Waal Malefijt R, Huijbens RJ, de Vries JE, Figdor CG . IL-10 stimulates monocyte Fc gamma R surface expression and cytotoxic activity. Distinct regulation of antibody-dependent cellular cytotoxicity by IFN-gamma, IL-4, and IL-10. J Immunol 1992; 149: 4048–4052.

    CAS  PubMed  Google Scholar 

  11. Ho AS, Liu Y, Khan TA, Hsu DH, Bazan JF, Moore KW . A receptor for interleukin 10 is related to interferon receptors. Proc Natl Acad Sci USA 1993; 90: 11267–11271.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kotenko SV, Krause CD, Izotova LS, Pollack BP, Wu W, Pestka S . Identification and functional characterization of a second chain of the interleukin-10 receptor complex. EMBO J 1997; 16: 5894–5903.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Finbloom DS, Winestock KD . IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes. J Immunol 1995; 155: 1079–1090.

    CAS  PubMed  Google Scholar 

  14. Wehinger J, Gouilleux F, Groner B, Finke J, Mertelsmann R, Weber-Nordt RM . IL-10 induces DNA binding activity of three STAT proteins (Stat1, Stat3, and Stat5) and their distinct combinatorial assembly in the promoters of selected genes. FEBS Lett 1996; 394: 365–370.

    Article  CAS  PubMed  Google Scholar 

  15. Volk H, Asadullah K, Gallagher G, Sabat R, Grutz G . IL-10 and its homologs: important immune mediators and emerging immunotherapeutic targets. Trends Immunol 2001; 22: 414–417.

    Article  CAS  PubMed  Google Scholar 

  16. Renauld JC . Class II cytokine receptors and their ligands: key antiviral and inflammatory modulators. Nat Rev Immunol 2003; 3: 667–676.

    Article  CAS  PubMed  Google Scholar 

  17. Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher PB . Interleukin-10 and related cytokines and receptors. Annu Rev Immunol 2004; 22: 929–979.

    Article  CAS  PubMed  Google Scholar 

  18. 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: 1814–1819.

    Article  CAS  PubMed  Google Scholar 

  19. 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: 5397–5402.

    Article  CAS  PubMed  Google Scholar 

  20. Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R . IL-22 increases the innate immunity of tissues. Immunity 2004; 21: 241–254.

    Article  CAS  PubMed  Google Scholar 

  21. Dumoutier L, Van Roost E, Colau D, Renauld JC . Human interleukin-10-related T cell-derived inducible factor: molecular cloning and functional characterization as an hepatocyte-stimulating factor. Proc Natl Acad Sci USA 2000; 97: 10144–10149.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Radaeva S, Sun R, Pan HN, Hong F, Gao B . 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 2004; 39: 1332–1342.

    Article  CAS  PubMed  Google Scholar 

  23. 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 2001; 21: 1047–1053.

    Article  CAS  PubMed  Google Scholar 

  24. Xie MH, Aggarwal S, Ho WH 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: 31335–31339.

    Article  CAS  PubMed  Google Scholar 

  25. Kotenko SV, Izotova LS, Mirochnitchenko OV et al. 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 2001; 276: 2725–2732.

    Article  CAS  PubMed  Google Scholar 

  26. 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: 33676–33682.

    Article  CAS  PubMed  Google Scholar 

  27. 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: 7090–7095.

    Article  CAS  PubMed  Google Scholar 

  28. Kotenko SV, Izotova LS, Mirochnitchenko OV et al. Identification, cloning, and characterization of a novel soluble receptor that binds IL-22 and neutralizes its activity. J Immunol 2001; 166: 7096–7103.

    Article  CAS  PubMed  Google Scholar 

  29. Xu W, Presnell SR, Parrish-Novak J et al. A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist. Proc Natl Acad Sci USA 2001; 98: 9511–9516.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Gruenberg BH, Schoenemeyer A, Weiss B et al. A novel, soluble homologue of the human IL-10 receptor with preferential expression in placenta. Genes Immun 2001; 2: 329–334.

    Article  CAS  PubMed  Google Scholar 

  31. Dumoutier L, Leemans C, Lejeune D, Kotenko SV, Renauld JC . Cutting edge: STAT activation by IL-19, IL-20 and mda-7 through IL-20 receptor complexes of two types. J Immunol 2001; 167: 3545–3549.

    Article  CAS  PubMed  Google Scholar 

  32. Parrish-Novak J, Xu W, Brender T et al. Interleukins 19, 20, and 24 signal through two distinct receptor complexes. Differences in receptor-ligand interactions mediate unique biological functions. J Biol Chem 2002; 277: 47517–47523.

    Article  CAS  PubMed  Google Scholar 

  33. Sheppard P, Kindsvogel W, Xu W et al. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol 2003; 4: 63–68.

    Article  CAS  PubMed  Google Scholar 

  34. Kotenko SV, Gallagher G, Baurin VV et al. IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol 2003; 4: 69–77.

    Article  CAS  PubMed  Google Scholar 

  35. Sheikh F, Baurin VV, Lewis-Antes A et al. Cutting edge: IL-26 signals through a novel receptor complex composed of IL-20 receptor 1 and IL-10 receptor 2. J Immunol 2004; 172: 2006–2010.

    Article  CAS  PubMed  Google Scholar 

  36. Josephson K, Logsdon NJ, Walter MR . Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site. Immunity 2001; 15: 35–46.

    Article  CAS  PubMed  Google Scholar 

  37. Reineke U, Sabat R, Volk HD, Schneider-Mergener J . Mapping of the interleukin-10/interleukin-10 receptor combining site. Protein Sci 1998; 7: 951–960.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Nagem RA, Colau D, Dumoutier L, Renauld JC, Ogata C, Polikarpov I . Crystal structure of recombinant human interleukin-22. Structure (Camb) 2002; 10: 1051–1062.

    Article  CAS  Google Scholar 

  39. Reineke U, Schneider-Mergener J, Glaser RW et al. Evidence for conformationally different states of interleukin-10: binding of a neutralizing antibody enhances accessibility of a hidden epitope. J Mol Recognit 1999; 12: 242–248.

    Article  CAS  PubMed  Google Scholar 

  40. Logsdon NJ, Jones BC, Josephson K, Cook J, Walter MR . Comparison of interleukin-22 and interleukin-10 soluble receptor complexes. J Interferon Cytokine Res 2002; 22: 1099–1112.

    Article  CAS  PubMed  Google Scholar 

  41. Pletnev S, Magracheva E, Kozlov S et al. Characterization of the recombinant extracellular domains of human interleukin-20 receptors and their complexes with interleukin-19 and interleukin-20. Biochemistry 2003; 42: 12617–12624.

    Article  CAS  PubMed  Google Scholar 

  42. Li J, Tomkinson KN, Tan XY et al. Temporal associations between interleukin 22 and the extracellular domains of IL-22R and IL-10R2. Int Immunopharmacol 2004; 4: 693–708.

    Article  CAS  PubMed  Google Scholar 

  43. Walter MR, Windsor WT, Nagabhushan TL et al. Crystal structure of a complex between interferon-gamma and its soluble high-affinity receptor. Nature 1995; 376: 230–235.

    Article  CAS  PubMed  Google Scholar 

  44. Wolk K, Docke WD, von Baehr V, Volk HD, Sabat R . Impaired antigen presentation by human monocytes during endotoxin tolerance. Blood 2000; 96: 218–223.

    CAS  PubMed  Google Scholar 

  45. Reineke U . Antibody epitope mapping using arrays of synthetic peptides. Methods Mol Biol 2004; 248: 443–463.

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Annette Buβ, Christa Liebenthal, and Michaela Nieter for excellent technical assistance. We also thank Elizabeth Wallace for accurately proofreading the manuscript.

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Authors and Affiliations

  1. Interdisciplinary Group of Molecular Immunopathology, Dermatology Medical, Immunology, University Hospital Charité, Berlin, Germany

    K Wolk, E Witte, K Witte, M Friedrich & R Sabat

  2. Jerini AG, Berlin, Germany

    U Reineke

  3. Department of Dermatology, University Hospital Charité, Berlin, Germany

    W Sterry

  4. CRBA Dermatology, Schering AG, Berlin, Germany

    K Asadullah

  5. Institute of Medical Immunology, University Hospital Charité, Berlin, Germany

    H-D Volk

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Correspondence to R Sabat.

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Wolk, K., Witte, E., Reineke, U. et al. Is there an interaction between interleukin-10 and interleukin-22?. Genes Immun 6, 8–18 (2005). https://doi.org/10.1038/sj.gene.6364144

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