IL-33 and ST2 in atopic dermatitis: expression profiles and modulation by triggering factors

J Invest Dermatol. 2012 May;132(5):1392-400. doi: 10.1038/jid.2011.446. Epub 2012 Jan 26.

Abstract

In the acute phase of atopic dermatitis (AD), T-helper type 2 (Th2) cytokines characterize the inflammatory response in the skin. IL-33 is a new tissue-derived cytokine, which is mainly expressed by cells of barrier tissues, and is known to activate Th2 lymphocytes, mast cells, and eosinophils. IL-33 signals through a receptor complex consisting of IL-33-specific receptor ST2 and a co-receptor IL-1RAcP. As IL-33 is known to promote Th2-type immunity, we examined expression profiles of IL-33 and its receptor components in human AD skin, in the murine model of AD, and in various cell models. We found increased expression of IL-33 and ST2 in AD skin after allergen or staphylococcal enterotoxin B (SEB) exposure, as well as in the skin of 22-week-old filaggrin-deficient mice. In addition, skin fibroblasts, HaCaT keratinocytes, primary macrophages, and HUVEC endothelial cells efficiently produced IL-33 in response to the combined stimulation of tumor necrosis factor-α and IFN-γ, which was further enhanced by a mimetic of double-stranded RNA. Finally, the increased expression of IL-33 and ST2 caused by irritant, allergen, or SEB challenge was suppressed by topical tacrolimus treatment. These results suggest an important role for IL-33-ST2 interaction in AD and highlight the fact that bacterial and viral infections may increase the production of IL-33.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology
  • Animals
  • Cells, Cultured
  • Dermatitis, Atopic / genetics
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / metabolism*
  • Disease Models, Animal
  • Enterotoxins / immunology
  • Female
  • Fibroblasts / metabolism
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Interferon-gamma / pharmacology
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins / metabolism*
  • Intermediate Filament Proteins / genetics
  • Keratinocytes / metabolism
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Pyroglyphidae / immunology
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / metabolism*
  • Tacrolimus / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation

Substances

  • Allergens
  • Enterotoxins
  • IL1RL1 protein, human
  • IL33 protein, human
  • Immunosuppressive Agents
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins
  • Intermediate Filament Proteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • Tumor Necrosis Factor-alpha
  • filaggrin
  • enterotoxin B, staphylococcal
  • Interferon-gamma
  • Tacrolimus