title: CCR4 and CCR10 are expressed on epidermal keratinocytes and are involved in cutaneous immune reaction.
abstract: CC chemokine ligand (CCL)17 and CCL27 produced by epidermal keratinocytes (KCs) recruit CC chemokine receptor (CCR)4 and CCR10 expressing T cells into the skin, respectively, resulting in enhanced skin inflammation. However, CCR4/CCL17 and CCR10/CCL27 interactions in epidermal KCs have not been investigated. The purpose of this study was to evaluate the role of the CCR4/CCL17 and CCR10/CCL27 loops in cutaneous immune reaction. Normal human KCs (NHKs) and HaCaT KCs expressed both CCR4 and CCR10 at mRNA and protein levels. CCR4 ligand CCL17 but not CCR10 ligand CCL27 induced production of IL-12 p40, granulocyte/monocyte colony-stimulating factor (GM-CSF) and nerve growth factor (NGF) by KCs. Both CCL17 and CCL27 induced migration of KCs in Boyden chamber assay and wound scratch assay. This study revealed that CCR4 and CCR10 are expressed on epidermal KCs and that both are functional in terms of skin cytokine production and/or migration to their ligand CCL17 and CCL27, respectively. Thus this study provided new insight into chemokine/chemokine receptors of KCs.
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Seiki
authors.initials: S
authors.lastname: Fujimoto
authors.forename: Hideya
authors.initials: H
authors.lastname: Uratsuji
authors.forename: Hidehisa
authors.initials: H
authors.lastname: Saeki
authors.forename: Shinji
authors.initials: S
authors.lastname: Kagami
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Tsunemi
authors.forename: Mayumi
authors.initials: M
authors.lastname: Komine
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Tamaki
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D054414:Chemokine CCL17 / Q000502:physiology; D054425:Chemokine CCL27 / Q000502:physiology; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism*; D008297:Male; D020932:Nerve Growth Factor / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D054447:Receptors, CCR10 / Q000096:biosynthesis*; D054398:Receptors, CCR4 / Q000096:biosynthesis*
chemical_list: C106230:CCL17 protein, human; C492276:CCL27 protein, human; C515706:CCR10 protein, human; C515354:CCR4 protein, human; D054414:Chemokine CCL17; D054425:Chemokine CCL27; D012333:RNA, Messenger; D054447:Receptors, CCR10; D054398:Receptors, CCR4; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020932:Nerve Growth Factor