title: CCL1-CCR8 interactions: an axis mediating the recruitment of T cells and Langerhans-type dendritic cells to sites of atopic skin inflammation.
abstract: Atopic dermatitis represents a chronically relapsing skin disease with a steadily increasing prevalence of 10-20% in children. Skin-infiltrating T cells, dendritic cells (DC), and mast cells are thought to play a crucial role in its pathogenesis. We report that the expression of the CC chemokine CCL1 (I-309) is significantly and selectively up-regulated in atopic dermatitis in comparison to psoriasis, cutaneous lupus erythematosus, or normal skin. CCL1 serum levels of atopic dermatitis patients are significantly higher than levels in healthy individuals. DC, mast cells, and dermal endothelial cells are abundant sources of CCL1 during atopic skin inflammation and allergen challenge, and Staphylococcus aureus-derived products induce its production. In vitro, binding and cross-linking of IgE on mast cells resulted in a significant up-regulation of this inflammatory chemokine. Its specific receptor, CCR8, is expressed on a small subset of circulating T cells and is abundantly expressed on interstitial DC, Langerhans cells generated in vitro, and their monocytic precursors. Although DC maintain their CCR8+ status during maturation, brief activation of circulating T cells recruits CCR8 from intracytoplamic stores to the cell surface. Moreover, the inflammatory and atopy-associated chemokine CCL1 synergizes with the homeostatic chemokine CXCL12 (SDF-1alpha) resulting in the recruitment of T cell and Langerhans cell-like DC. Taken together, these findings suggest that the axis CCL1-CCR8 links adaptive and innate immune functions that play a role in the initiation and amplification of atopic skin inflammation.
authors.affiliation: Department of Dermatology, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gombert
authors.forename: Marie-Caroline
authors.initials: MC
authors.lastname: Dieu-Nosjean
authors.forename: Franziska
authors.initials: F
authors.lastname: Winterberg
authors.forename: Erich
authors.initials: E
authors.lastname: Bünemann
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kubitza
authors.forename: Ludivine
authors.initials: L
authors.lastname: Da Cunha
authors.forename: Anna
authors.initials: A
authors.lastname: Haahtela
authors.forename: Sari
authors.initials: S
authors.lastname: Lehtimäki
authors.forename: Anja
authors.initials: A
authors.lastname: Müller
authors.forename: Juliane
authors.initials: J
authors.lastname: Rieker
authors.forename: Stephan
authors.initials: S
authors.lastname: Meller
authors.forename: Andor
authors.initials: A
authors.lastname: Pivarcsi
authors.forename: Andrea
authors.initials: A
authors.lastname: Koreck
authors.forename: Wolf-Herman
authors.initials: WH
authors.lastname: Fridman
authors.forename: Hans-Walter
authors.initials: HW
authors.lastname: Zentgraf
authors.forename: Hermann
authors.initials: H
authors.lastname: Pavenstädt
authors.forename: Ali
authors.initials: A
authors.lastname: Amara
authors.forename: Christophe
authors.initials: C
authors.lastname: Caux
authors.forename: Lajos
authors.initials: L
authors.lastname: Kemeny
authors.forename: Harri
authors.initials: H
authors.lastname: Alenius
authors.forename: Antti
authors.initials: A
authors.lastname: Lauerma
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruzicka
authors.forename: Albert
authors.initials: A
authors.lastname: Zlotnik
authors.forename: Bernhard
authors.initials: B
authors.lastname: Homey
mesh_terms: D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D000942:Antigens, Bacterial; D016022:Case-Control Studies; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D054402:Chemokine CCL1; D054414:Chemokine CCL17; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000097:blood / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism; D002648:Child; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology* / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000473:pathology; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D011565:Psoriasis / Q000276:immunology / Q000473:pathology; D054401:Receptors, CCR8; D019707:Receptors, Chemokine / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D000485:Allergens; D000942:Antigens, Bacterial; C065971:CCL1 protein, human; C106230:CCL17 protein, human; C103330:CCR8 protein, human; C515255:CXCL12 protein, human; C502258:Ccl1 protein, mouse; C499538:Ccl17 protein, mouse; D054402:Chemokine CCL1; D054414:Chemokine CCL17; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D016207:Cytokines; D018836:Inflammation Mediators; D054401:Receptors, CCR8; D019707:Receptors, Chemokine; D007073:Immunoglobulin E