Brief Definitive Report

Requirement for the Chemokine Receptor CCR6 in Allergic Pulmonary Inflammation

Correspondence to: Donald N. Cook, Pulmonary Division, Duke University Medical Center, Box 2629, Medical Sciences Research Building, Durham, NC 27710. Tel:919-668-5201 Fax:919-668-0494 E-mail:cook0054{at}mc.duke.edu.

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)-3 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-3, 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-3 and CCR6 function in allergic pulmonary responses and suggest that these molecules might represent novel therapeutic targets for treatment of asthma.

Key Words: CCR6, MIP-3, chemokine, asthma, lung

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