title: CD40 expression on antigen presenting cells and correlation with disease severity in atopic dermatitis.
abstract: Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with cutaneous hyperreactivity to environmental stimuli, resulting in increased infiltration of inflammatory cells, IgE production and enhanced expression of various co-stimulatory molecules, Th2 cytokines and chemokines. Antigen presenting cells (APCs) are critical for AD disease pathogenesis and interaction between APCs and inflammatory T cells represents an important signal required for induction and maintenance of the inflammatory process. CD40 was shown to be upregulated on inflammatory cells in patients with atopic dermatitis; however the identity of these cells and their correlation with disease severity remained unknown. To address these questions, we determined CD40 expression in skin lesions and on peripheral blood cells from AD patients and identified a positive correlation between the numbers of CD40 positive cells and disease severity. Furthermore, we identified the nature of CD40 positive cells in skin lesions to include CD1a+ and CD11b+ APCs. Finally, a correlation between serum PARC and IgE levels and the numbers of CD40+ cells in AD skin lesions was found. Combined, these findings demonstrate that CD40 is upregulated on APCs, cell types previously shown to contribute to AD disease pathology, and suggest that therapeutic strategies targeting CD40 positive cells may provide benefit to AD patients.
authors.affiliation: Department of Preclinical Therapeutics, Seattle Genetics, Inc., Bothell, WA 98021, USA. eoflazoglu@seagen.com
authors.forename: Ezogelin
authors.initials: E
authors.lastname: Oflazoglu
authors.forename: Eric L
authors.initials: EL
authors.lastname: Simpson
authors.forename: Rodd
authors.initials: R
authors.lastname: Takiguchi
authors.forename: Jon M
authors.initials: JM
authors.lastname: Hanifin
authors.forename: Iqbal S
authors.initials: IS
authors.lastname: Grewal
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Gerber
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology*; D019013:CD40 Antigens / Q000096:biosynthesis*; D003876:Dermatitis, Atopic / Q000276:immunology*; D006801:Humans; D012720:Severity of Illness Index
chemical_list: D019013:CD40 Antigens