title: CX₃CL1 (fractalkine) and its receptor CX₃CR1 regulate atopic dermatitis by controlling effector T cell retention in inflamed skin.
abstract: Atopic dermatitis (AD) is a chronic allergic dermatosis characterized by epidermal thickening and dermal inflammatory infiltrates with a dominant Th2 profile during the acute phase, whereas a Th1 profile is characteristic of the chronic stage. Among chemokines and chemokine receptors associated with inflammation, increased levels of CX3CL1 (fractalkine) and its unique receptor, CX3CR1, have been observed in human AD. We have thus investigated their role and mechanism of action in experimental models of AD and psoriasis. AD pathology and immune responses, but not psoriasis, were profoundly decreased in CX3CR1-deficient mice and upon blocking CX3CL1-CX3CR1 interactions in wild-type mice. CX3CR1 deficiency affected neither antigen presentation nor T cell proliferation in vivo upon skin sensitization, but CX3CR1 expression by both Th2 and Th1 cells was required to induce AD. Surprisingly, unlike in allergic asthma, where CX3CL1 and CX3CR1 regulate the pathology by controlling effector CD4(+) T cell survival within inflamed tissues, adoptive transfer experiments established CX3CR1 as a key regulator of CD4(+) T cell retention in inflamed skin, indicating a new function for this chemokine receptor. Therefore, although CX3CR1 and CX3CL1 act through distinct mechanisms in different pathologies, our results further indicate their interest as promising therapeutic targets in allergic diseases.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, France European Genomic Institute of Diabetes, 59045 Lille, France Department of Dermatology, Claude-Huriez Hospital, 59037 Lille, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Staumont-Sallé
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, France European Genomic Institute of Diabetes, 59045 Lille, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Fleury
authors.affiliation: Centre National de la Recherche Scientifique UMR7275, Université Nice Sophia Antipolis, 06560 Valbonne, France Centre National de la Recherche Scientifique UMR7275, Université Nice Sophia Antipolis, 06560 Valbonne, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Lazzari
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, France European Genomic Institute of Diabetes, 59045 Lille, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Molendi-Coste
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, France Department of Dermatology, Claude-Huriez Hospital, 59037 Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Hornez
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, France Department of Dermatology, Claude-Huriez Hospital, 59037 Lille, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Lavogiez
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, France European Genomic Institute of Diabetes, 59045 Lille, France.
authors.forename: Akira
authors.initials: A
authors.lastname: Kanda
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, France European Genomic Institute of Diabetes, 59045 Lille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Wartelle
authors.affiliation: Centre National de la Recherche Scientifique UMR7275, Université Nice Sophia Antipolis, 06560 Valbonne, France Centre National de la Recherche Scientifique UMR7275, Université Nice Sophia Antipolis, 06560 Valbonne, France.
authors.forename: Anissa
authors.initials: A
authors.lastname: Fries
authors.affiliation: Center of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, 80802 Munich, Germany.
authors.forename: Davide
authors.initials: D
authors.lastname: Pennino
authors.affiliation: Centre National de la Recherche Scientifique UMR7275, Université Nice Sophia Antipolis, 06560 Valbonne, France Centre National de la Recherche Scientifique UMR7275, Université Nice Sophia Antipolis, 06560 Valbonne, France.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Mionnet
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, France European Genomic Institute of Diabetes, 59045 Lille, France.
authors.forename: Janne
authors.initials: J
authors.lastname: Prawitt
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, France European Genomic Institute of Diabetes, 59045 Lille, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bouchaert
authors.affiliation: Department of Dermatology, Claude-Huriez Hospital, 59037 Lille, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Delaporte
authors.affiliation: Centre National de la Recherche Scientifique UMR7275, Université Nice Sophia Antipolis, 06560 Valbonne, France Centre National de la Recherche Scientifique UMR7275, Université Nice Sophia Antipolis, 06560 Valbonne, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Glaichenhaus
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, France European Genomic Institute of Diabetes, 59045 Lille, France.
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.affiliation: Centre National de la Recherche Scientifique UMR7275, Université Nice Sophia Antipolis, 06560 Valbonne, France Centre National de la Recherche Scientifique UMR7275, Université Nice Sophia Antipolis, 06560 Valbonne, France david.dombrowicz@pasteur-lille.fr vjulia@ipmc.cnrs.fr.
authors.forename: Valérie
authors.initials: V
authors.lastname: Julia
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, France European Genomic Institute of Diabetes, 59045 Lille, France david.dombrowicz@pasteur-lille.fr vjulia@ipmc.cnrs.fr.
authors.forename: David
authors.initials: D
authors.lastname: Dombrowicz
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D049109:Cell Proliferation; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009841:Oligonucleotides / Q000235:genetics / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology*; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; C515539:Cx3cl1 protein, mouse; C471885:Cx3cr1 protein, mouse; D009841:Oligonucleotides; D019707:Receptors, Chemokine