Allergic asthma is a common chronic Th2-driven airway inflammatory disease. TSLP is an epithelium-derived cytokine recognized as a potent factor in the development of asthma. TSLP is known to influence the function of dendritic cells to enhance Th2 T cell responses, however many of the mechanisms underlying TSLP-induced airway inflammation remain undefined. In addition to dendritic cells, the lung tissues include other MHC class II-expressing phagocytic populations which may influence T cell responses. Among these potential antigen-presenting cells are macrophage subsets (including CD11c+ SiglecF+ F4/80+ resident tissue macrophages and CD11c-lo CD11b+ F4/80+ non-tissue macrophages) which can comprise up to 10% of hematopoietic cells in the lung during airway inflammation. Here we demonstrate that these pulmonary macrophage populations express the TSLP receptor and non-tissue macrophages are rapidly recruited to the lung tissue in response airway priming in the context of TSLP. Blockade of CCR2- and/or CX3CR1-dependent recruitment of non-tissue macrophages diminishes eosinophilic allergic airway inflammation and expression of type II inflammatory genes. These finding suggest a crucial role for non-tissue macrophages in the development of TSLP-mediated airway inflammation. By elucidating the cellular mechanisms of airway inflammation, this data will contribute to more effective therapeutic approaches for treatment of asthmatic disease.
- Copyright © 2013 by The American Association of Immunologists, Inc.