Requirement for the chemokine receptor CCR6 in allergic pulmonary inflammation.
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.
Lukacs
N W
NW
Department of Immunology, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Prosser
D M
DM
Wiekowski
M
M
Lira
S A
SA
Cook
D N
DN
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
C106311:CCR6 protein, human; D016207:Cytokines; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D007073:Immunoglobulin E