title: Requirement for the chemokine receptor CCR6 in allergic pulmonary inflammation.
abstract: Allergic asthmatic responses in the airway are associated with airway hyperreactivity, eosinophil accumulation in the lung, and cytokine production by allergen-specific, T helper cell type 2 (Th2) lymphocytes. Here, we show that in a cockroach antigen (CA) model of allergic pulmonary inflammation, the chemokine macrophage inflammatory protein (MIP)-3alpha is expressed in the lung within hours of allergen challenge. To determine the biologic relevance of this expression, mice lacking CCR6, the only known receptor for MIP-3alpha, were studied for their response to CA. CCR6-deficient mice were immunized to the same extent as their wild-type counterparts, as judged by cytokine production in antigen-challenged lymphocytes. However, compared with CA-challenged wild-type mice, challenged CCR6-deficient mice had reduced airway resistance, fewer eosinophils around the airway, lower levels of interleukin 5 in the lung, and reduced serum levels of immunoglobulin E. Together, these data demonstrate that MIP-3alpha and CCR6 function in allergic pulmonary responses and suggest that these molecules might represent novel therapeutic targets for treatment of asthma.
authors.affiliation: Department of Immunology, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
authors.forename: N W
authors.initials: NW
authors.lastname: Lukacs
authors.forename: D M
authors.initials: DM
authors.lastname: Prosser
authors.forename: M
authors.initials: M
authors.lastname: Wiekowski
authors.forename: S A
authors.initials: SA
authors.lastname: Lira
authors.forename: D N
authors.initials: DN
authors.lastname: Cook
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D007073:Immunoglobulin E / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: C106311:CCR6 protein, human; D016207:Cytokines; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D007073:Immunoglobulin E