IL-33 induces skin inflammation with mast cell and neutrophil activation

Eur J Immunol. 2011 Aug;41(8):2229-37. doi: 10.1002/eji.201041360. Epub 2011 Jun 24.


Psoriasis is a common chronic autoimmune condition of the skin characterized by hyperplasia of epidermal keratinocytes associated with pro-inflammatory cytokines. IL-33 is a new member of the IL-1 superfamily that signals through the ST2 receptor and was originally defined as an inducer of T helper 2 (Th2) cytokines. Recently, broader immune activatory potential has been defined for IL-33 particularly via mast cell activation and neutrophil migration. Here, we show that ST2(-/-) mice exhibit reduced cutaneous inflammatory responses compared with WT mice in a phorbol ester-induced model of skin inflammation. Furthermore, injections of IL-33 into the ears of mice induce an inflammatory skin lesion. This inflammatory response was partially dependent on mast cells as mast cell-deficient mice (Kit(W-sh/W-sh) ) showed delayed responses to IL-33. IL-33 also recruited neutrophils to the ear, an effect mediated in part by increased production of the chemokine KC (CXCL1). Finally, we show that IL-33 expression is up-regulated in the epidermis of clinical psoriatic lesions, compared with healthy skin. These results therefore demonstrate that IL-33 may play a role in psoriasis-like plaque inflammation. IL-33 targeting may provide a new treatment strategy for psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CXCL1 / immunology
  • Chemokine CXCL1 / metabolism
  • Dermatitis / etiology
  • Dermatitis / immunology*
  • Flow Cytometry
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins / immunology*
  • Interleukins / metabolism
  • Interleukins / toxicity
  • Male
  • Mast Cells / immunology*
  • Mast Cells / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophil Activation / immunology
  • Neutrophil Infiltration / immunology
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • Psoriasis / immunology
  • Psoriasis / metabolism
  • Receptors, Interleukin / deficiency
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / immunology
  • Skin / immunology
  • Skin / metabolism
  • Skin / pathology
  • Tetradecanoylphorbol Acetate / toxicity


  • Chemokine CXCL1
  • Cxcl1 protein, mouse
  • IL33 protein, human
  • Il1rl1 protein, mouse
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins
  • Receptors, Interleukin
  • Tetradecanoylphorbol Acetate