title: Requirement for chemokine receptor 5 in the development of allergen-induced airway hyperresponsiveness and inflammation.
abstract: Chemokine receptor (CCR) 5 is expressed on dendritic cells, macrophages, CD8 cells, memory CD4 T cells, and stromal cells, and is frequently used as a marker of T helper type 1 cells. Interventions that abrogate CCR5 or interfere with its ligand binding have been shown to alter T helper type 2-induced inflammatory responses. The role of CCR5 on allergic airway responses is not defined. CCR5-deficient (CCR5(-/-)) and wild-type (CCR5(+/+)) mice were sensitized and challenged with ovalbumin (OVA) and allergic airway responses were monitored 48 hours after the last OVA challenge. Cytokine levels in lung cell culture supernatants were also assessed. CCR5(-/-) mice showed significantly lower airway hyperresponsiveness (AHR) and lower numbers of total cells, eosinophils, and lymphocytes in bronchoalveolar lavage (BAL) fluid compared with CCR5(+/+) mice after sensitization and challenge. The levels of IL-4 and IL-13 in BAL fluid of CCR5(-/-) mice were lower than in CCR5(+/+) mice. Decreased numbers of lung T cells were also detected in CCR5(-/-) mice after sensitization and challenge. Transfer of OVA-sensitized T cells from CCR5(+/+), but not transfer of CCR5(-/-) cells, into CCR5(-/-) mice restored AHR and numbers of eosinophils in BAL fluid after OVA challenge. Accordingly, the numbers of airway-infiltrating donor T cells were significantly higher in the recipients of CCR5(+/+) T cells. Taken together, these data suggest that CCR5 plays a pivotal role in allergen-induced AHR and airway inflammation, and that CCR5 expression on T cells is essential to the accumulation of these cells in the airways.
authors.affiliation: Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical sciences, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Fuchimoto
authors.forename: Arihiko
authors.initials: A
authors.lastname: Kanehiro
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Miyahara
authors.forename: Hikari
authors.initials: H
authors.lastname: Koga
authors.forename: Genyo
authors.initials: G
authors.lastname: Ikeda
authors.forename: Koichi
authors.initials: K
authors.lastname: Waseda
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tanimoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ueha
authors.forename: Mikio
authors.initials: M
authors.lastname: Kataoka
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
mesh_terms: D000485:Allergens / Q000633:toxicity*; D000818:Animals; D018893:Bronchoalveolar Lavage; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D018793:Interleukin-13 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D000485:Allergens; D018793:Interleukin-13; D019713:Receptors, CCR5; D015847:Interleukin-4