Crucial role for CD11c+ interstitial macrophages in the development of TSLP-mediated allergic airway inflammation (HYP2P.321)

Abstract

Abstract Allergic asthma is a common chronic Th2-driven airway inflammatory disease. TSLP is an epithelial-derived cytokine recognized as a potent factor in the development of asthma. TSLP is known to influence the ability 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 that may influence T cell responses. Here we demonstrate that pulmonary CD11c+ interstitial macrophages (IM) (CD11cintF4/80+Nur77+CD11b+CX3CR1hiCCR2loMHCII+/-) express high levels of TSLPR and recruited to the lung tissue in response airway priming in the context of TSLP and antigen. TSLP-mediated eosinophilic allergic airway inflammation is attenuated by ablation of CD11c+ IM or by selective deficiency of TSLPR signaling in these cells. More importantly, CD11c+ IM are sufficient for the development of this response in the absence of DC. These findings indicate a crucial role for CD11c+ IM in the development of TSLP-mediated allergic airway inflammation. By elucidating the cellular mechanisms of airway inflammation, these data may contribute to more effective therapeutic approaches for treatment of asthmatic disease.