Blocking TGF beta via Inhibition of the alpha v beta 6 Integrin: A Possible Therapy for Systemic Sclerosis Interstitial Lung Disease

Interstitial lung disease (ILD) is a commonly encountered complication of systemic sclerosis (SSc) and accounts for a significant proportion of SSc-associated morbidity and mortality. Its pathogenesis remains poorly understood, and therapies that treat SSc ILD are suboptimal, at best. SSc ILD pathogenesis may share some common mechanisms with other fibrotic lung diseases, in which dysregulation of lung epithelium can contribute to pathologic fibrosis via recruitment or in situ generation and activation of fibroblasts. TGF beta, a master regulator of fibrosis, is tightly regulated in the lung by the integrin alpha v beta 6, which is expressed at low levels on healthy alveolar epithelial cells but is highly induced in the setting of lung injury or fibrosis. Here we discuss the biology of alpha v beta 6 and present this integrin as a potentially attractive target for inhibition in the setting of SSc ILD.