Expression of constitutively active TβRI leads to attenuation of ovalbumin-induced allergic airway inflammation associated with augmented M2 polarization of alveolar macrophage

Abstract

Background: Transforming growth factor-β (Tgf-β) plays an important role in the pathogenesis of asthma through the regulation of T cells and airway epithelium. Its functions in alveolar macrophage (AM) during allergic airway inflammation remain unknown.

Methods: A murine asthma model was induced with ovalbumin (ova) in TβRI^CA/Fsp1-Cre transgenic mice expressing constitutively active Tgf-β receptor type I (TβRI^CA) under the control of Fsp1-Cre transgene. Cells in the bronchoalveolar lavage (BAL) were collected to study immune cell infiltration in the lungs. Cytokine levels in BAL fluid were measured by enzyme-linked immunoassay (ELISA). Lungs were sectioned and stained with hematoxylin and eosin, periodic acid-Schiff, and trichrome for histopathologic evaluation. AMs were assessed by flow cytometry and were sorted for quantitative polymerase chain reaction analysis.

Results: Our data indicated that TβRI^CA transcripts were induced in AMs of TβRI^CA/Fsp1-Cre mice. Following the ova challenges, TβRI^CA/Fsp1-Cre mice exhibited reduced cellular infiltration of the airway, reduced pulmonary fibrosis, and reduced bronchial mucus secretion as compared to ova-challenged wild-type mice. An alternatively activated macrophage (M2) polarization was significantly elevated in the lungs of ova-challenged TβRI^CA/Fsp1-Cre mice as reflected by increased numbers of AMs expressing M2 subtype marker, CD163, in the lungs and enhanced expression of CCR2 and CD206 in AMs. Moreover, TβRI^CA/Fsp1-Cre AMs showed augmented expression of transcription factors, Foxo1, and IRF4, which are known to be positive regulators for M2 polarization.

Conclusions: Expression of TβRI^CA in AMs promoted M2 polarization and ameliorated allergic airway inflammation in an ova-induced asthma mouse model.

Keywords: Airway inflammation; Asthma; Macrophage; Tgf-β.