title: IL-23 induces atopic dermatitis-like inflammation instead of psoriasis-like inflammation in CCR2-deficient mice.
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.
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. sbromley@helix.mgh.harvard.edu
authors.forename: Shannon K
authors.initials: SK
authors.lastname: Bromley
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Larson
authors.forename: Steven F
authors.initials: SF
authors.lastname: Ziegler
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003876:Dermatitis, Atopic / Q000139:chemically induced*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D053759:Interleukin-23 / Q000009:adverse effects*; D015847:Interleukin-4 / Q000276:immunology; D008024:Ligands; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009504:Neutrophils / Q000276:immunology; D011565:Psoriasis / Q000139:chemically induced*; D054390:Receptors, CCR2 / Q000235:genetics*; D015398:Signal Transduction; D000094632:Thymic Stromal Lymphopoietin
chemical_list: C515335:Ccr2 protein, mouse; D016207:Cytokines; D053759:Interleukin-23; D008024:Ligands; D054390:Receptors, CCR2; D015847:Interleukin-4; D000094632:Thymic Stromal Lymphopoietin