The integrin receptor beta₇ subunit mediates airway remodeling and hyperresponsiveness in allergen exposed mice

Fibroblast differentiation to a myofibroblast phenotype is a feature of airway remodeling in asthma. Lung fibroblasts express the integrin receptor α₄β₇ and fibronectin induces myofibroblast differentiation via this receptor.

To investigate the role of the β7 integrin receptor subunit and α₄β₇ integrin complex in airway remodeling and airway hyperresponsiveness (AHR) in a murine model of chronic allergen exposure.

C57BL/6 wild type (WT) and β7 integrin null mice (β₇ -/-) were sensitized (days 1,10) and challenged with ovalbumin (OVA) three times a week for one or 4 weeks. Similar experiments were performed with WT mice in the presence or absence of α₄β₇ blocking antibodies. Bronchoalveolar (BAL) cell counts, AHR, histological evaluation, soluble collagen content, Transforming growth factor-β (TGFβ) and Interleukin-13 (IL13) were measured. Phenotype of fibroblasts cultured from WT and β₇ -/- saline (SAL) and OVA treated mice was evaluated.

Eosinophil numbers were similar in WT vs β7-/- mice. Prolonged OVA exposure in β7-/- mice was associated with reduced AHR, lung collagen content, peribronchial smooth muscle, lung tissue TGFβ and IL13 expression as compared to WT. Similar findings were observed in WT mice treated with α₄β₇ blocking antibodies. Fibroblast migration was enhanced in response to OVA in WT but not β7 -/- fibroblasts. α-SMA and fibronectin expression were reduced in β7-/- fibroblasts relative to WT.

The β7 integrin subunit and the α4β7 integrin complex modulate AHR and airway remodeling in a murine model of allergen exposure. This effect is, at least in part, explained by inhibition of fibroblast activation and is independent of eosinophilic inflammation.