title: A second step of chemotaxis after transendothelial migration: keratinocytes undergoing apoptosis release IFN-gamma-inducible protein 10, monokine induced by IFN-gamma, and IFN-gamma-inducible alpha-chemoattractant for T cell chemotaxis toward epidermis in atopic dermatitis.
abstract: Activation and skin-selective homing of T cells and their effector functions in the skin represent sequential immunological events in the pathogenesis of atopic dermatitis (AD). Apoptosis of keratinocytes, induced mainly by T cells and mediated by IFN-gamma and Fas, is the essential pathogenetic event in eczema formation. Keratinocyte apoptosis appears as activation-induced cell death in AD. By IFN-gamma stimulation, chemokines such as IFN-gamma-inducible protein 10, monokine induced by IFN-gamma, and IFN-gamma-inducible alpha-chemoattractant are strongly up-regulated in keratinocytes. These chemokines attract T cells bearing the specific receptor CXCR3, which is highly expressed on T cells isolated from skin biopsies of AD patients. Accordingly, an increased T cell chemotaxis was observed toward IFN-gamma-treated keratinocytes. Supporting these findings, enhanced IFN-gamma-inducible protein 10, monokine induced by IFN-gamma, and IFN-gamma-inducible alpha-chemoattractant expression was observed in lesional AD skin by immunohistochemical staining. These results indicate a second step of chemotaxis inside the skin after transendothelial migration of the inflammatory cells. Keratinocytes undergoing apoptosis in acute eczematous lesions release chemokines that attract more T cells toward the epidermis, which may further augment the inflammation and keratinocyte apoptosis.
authors.affiliation: Swiss Institute of Allergy and Asthma Research, Davos, Switzerland.
authors.forename: Sven
authors.initials: S
authors.lastname: Klunker
authors.forename: Axel
authors.initials: A
authors.lastname: Trautmann
authors.forename: Mübeccel
authors.initials: M
authors.lastname: Akdis
authors.forename: Johan
authors.initials: J
authors.lastname: Verhagen
authors.forename: Peter
authors.initials: P
authors.lastname: Schmid-Grendelmeier
authors.forename: Kurt
authors.initials: K
authors.lastname: Blaser
authors.forename: Cezmi A
authors.initials: CA
authors.lastname: Akdis
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000276:immunology*; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004727:Endothelium / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004817:Epidermis / Q000276:immunology / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000276:immunology
chemical_list: C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma