Limited Presence of IL-22 Binding Protein, a Natural IL-22 Inhibitor, Strengthens Psoriatic Skin Inflammation

J Immunol. 2017 May 1;198(9):3671-3678. doi: 10.4049/jimmunol.1700021. Epub 2017 Mar 29.


Psoriasis is a chronic inflammatory disease resulting from dysregulated immune activation associated with a large local secretion of cytokines. Among them, IL-22 largely contributes to epithelial remodeling and inflammation through inhibiting the terminal differentiation of keratinocytes and inducing antimicrobial peptides and selected chemokines. The activity of IL-22 is regulated by IL-22 binding protein (IL-22BP); however, the expression and role of IL-22BP in psoriatic skin has remained unknown so far. Here we showed that nonaffected skin of psoriasis patients displayed lower expression of IL-22BP than skin of healthy controls. Furthermore, the strong IL-22 increase in lesional psoriatic skin was accompanied by a moderate induction of IL-22BP. To investigate the role of IL-22BP in controlling IL-22 during skin inflammation, 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 antimicrobial peptides. We further recapitulated these findings in mice injected with an anti-IL-22BP neutralizing Ab. Hypothesizing that the IL-22/IL-22BP expression ratio reflects the level of bioactive IL-22 in psoriasis skin, we found positive correlations with the expression of IL-22-inducible molecules (IL-20, IL-24, IL-36γ, CXCL1, and BD2) in keratinocytes. Finally, we observed that serum IL-22/IL-22BP protein ratio strongly correlated with psoriasis severity. In conclusion, we propose that although IL-22BP can control deleterious actions of IL-22 in the skin, its limited production prevents a sufficient neutralization of IL-22 and contributes to the development and maintenance of epidermal alterations in psoriasis.

MeSH terms

  • Adult
  • Aged
  • Aminoquinolines
  • Animals
  • Antibodies, Blocking / administration & dosage
  • Cells, Cultured
  • Female
  • Gene Knockout Techniques
  • Humans
  • Imiquimod
  • Inflammation / immunology*
  • Interleukins / metabolism*
  • Keratinocytes / metabolism*
  • Keratinocytes / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Psoriasis / chemically induced
  • Psoriasis / immunology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / immunology
  • Receptors, Interleukin / metabolism*
  • Signal Transduction
  • Skin / immunology*
  • Young Adult


  • Aminoquinolines
  • Antibodies, Blocking
  • IL22RA2 protein, human
  • Interleukins
  • Receptors, Interleukin
  • interleukin-22 receptor
  • Imiquimod
  • interleukin-22