title: Absence of CCR4 exacerbates skin inflammation in an oxazolone-induced contact hypersensitivity model.
abstract: Chemokine receptor CCR4 is expressed by Th2 cells and is involved in the recruitment of inflammatory cells into the skin. We studied the effects of CCR4 deficiency in the murine model of oxazolone-induced contact hypersensitivity in CCR4-/- and wild-type (WT) mice. The inflammatory response in the skin at 24  hours post-elicitation was stronger in CCR4-/- mice compared with WT, evidenced by increased ear swelling and inflammatory cell infiltration. In addition, the mRNA expression levels of several cytokines, chemokines, chemokine receptors, and selectins in the skin of CCR4-/- mice were significantly elevated compared with WT mice. Time kinetic experiments during the sensitization and elicitation phases revealed that the number of CD3+CD4+ cells in CCR4-/- mice remained high longer during the sensitization phase and increased more rapidly during the elicitation phase compared with WT mice. These data demonstrate that the absence of CCR4 results in enhanced secondary immune response during allergic skin inflammation.
authors.affiliation: Unit of Excellence for Immunotoxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Lehtimäki
authors.forename: Sari
authors.initials: S
authors.lastname: Tillander
authors.forename: Anne
authors.initials: A
authors.lastname: Puustinen
authors.forename: Sampsa
authors.initials: S
authors.lastname: Matikainen
authors.forename: Tuula
authors.initials: T
authors.lastname: Nyman
authors.forename: Nanna
authors.initials: N
authors.lastname: Fyhrquist
authors.forename: Terhi
authors.initials: T
authors.lastname: Savinko
authors.forename: Marja-Leena
authors.initials: ML
authors.lastname: Majuri
authors.forename: Henrik
authors.initials: H
authors.lastname: Wolff
authors.forename: Harri
authors.initials: H
authors.lastname: Alenius
authors.forename: Antti
authors.initials: A
authors.lastname: Lauerma
mesh_terms: D000276:Adjuvants, Immunologic / Q000633:toxicity; D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D003872:Dermatitis / Q000276:immunology* / Q000503:physiopathology; D003877:Dermatitis, Contact / Q000276:immunology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004487:Edema / Q000276:immunology / Q000503:physiopathology; D018793:Interleukin-13 / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D010081:Oxazolone / Q000633:toxicity; D054398:Receptors, CCR4 / Q000235:genetics* / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D017252:CD3 Complex; D015704:CD4 Antigens; C515355:Ccr4 protein, mouse; D018793:Interleukin-13; D054398:Receptors, CCR4; D010081:Oxazolone