Editors' ChoiceLung Disease

Breathing Freely

Sci. Signal.  24 Jun 2014:
Vol. 7, Issue 331, pp. ec177
DOI: 10.1126/scisignal.2005615

Narrowing of the airways through accumulation of scar tissue and inflammation results from chronic injury in common diseases, such as COPD (chronic obstructive pulmonary disease) and severe chronic asthma. Such airway narrowing causes the obstruction responsible for the breathlessness that these patients experience, and there are no available treatments that ameliorate fibroinflammatory airway narrowing. Minagawa et al. engineered a monoclonal antibody that locks integrin αvβ8 in a specific inactive conformation. This integrin is required for activation of TGF-β (transforming growth factor–β), a central mediator of pathological inflammation and fibrosis. When administered to mice engineered to express only human and not mouse αvβ8, this antibody reduced airway inflammation and fibrosis in response to various injurious agents, including cigarette smoke and allergens that are involved in the pathogenesis of COPD.

S. Minagawa, J. Lou, R. I. Seed, A. Cormier, S. Wu, Y. Cheng, L. Murray, P. Tsui, J. Connor, R. Herbst, C. Govaerts, T. Barker, S. Cambier, H. Yanagisawa, A. Goodsell, M. Hashimoto, O. J. Brand, R. Cheng, R. Ma, K. J. McKnelly, W. Wen, A. Hill, D. Jablons, P. Wolters, H. Kitamura, J. Araya, A. J. Barczak, D. J. Erle, L. F. Reichardt, J. D. Marks, J. L. Baron, S. L. Nishimura, Selective targeting of TGF-β activation to treat fibroinflammatory airway disease. Sci. Transl. Med. 6, 241ra79 (2014). [PubMed]