IL-23 induces atopic dermatitis-like inflammation instead of psoriasis-like inflammation in CCR2-deficient mice

PLoS One. 2013;8(3):e58196. doi: 10.1371/journal.pone.0058196. Epub 2013 Mar 5.

Abstract

Psoriasis is an immune-mediated chronic inflammatory skin disease, characterized by epidermal hyperplasia and infiltration of leukocytes into the dermis and epidermis. IL-23 is expressed in psoriatic skin, and IL-23 injected into the skin of mice produces IL-22-dependent dermal inflammation and acanthosis. The chemokine receptor CCR2 has been implicated in the pathogenesis of several inflammatory diseases, including psoriasis. CCR2-positive cells and the CCR2 ligand, CCL2 are abundant in psoriatic lesions. To examine the requirement of CCR2 in the development of IL-23-induced cutaneous inflammation, we injected the ears of wild-type (WT) and CCR2-deficient (CCR2(-/-)) mice with IL-23. CCR2(-/-) mice had increased ear swelling and epidermal thickening, which was correlated with increased cutaneous IL-4 levels and increased numbers of eosinophils within the skin. In addition, TSLP, a cytokine known to promote and amplify T helper cell type 2 (Th2) immune responses, was also increased within the inflamed skin of CCR2(-/-) mice. Our data suggest that increased levels of TSLP in CCR2(-/-) mice may contribute to the propensity of these mice to develop increased Th2-type immune responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • Cytokines / immunology
  • Dermatitis, Atopic / chemically induced*
  • Disease Models, Animal
  • Eosinophils / immunology
  • Gene Expression Regulation
  • Humans
  • Inflammation / chemically induced*
  • Interleukin-23 / adverse effects*
  • Interleukin-4 / immunology
  • Ligands
  • Mast Cells / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neutrophils / immunology
  • Psoriasis / chemically induced*
  • Receptors, CCR2 / genetics*
  • Signal Transduction
  • Thymic Stromal Lymphopoietin

Substances

  • Ccr2 protein, mouse
  • Cytokines
  • Interleukin-23
  • Ligands
  • Receptors, CCR2
  • Interleukin-4
  • Thymic Stromal Lymphopoietin