Important lung pathologies such as chronic obstructive pulmonary disease (COPD) are caused by the coordinated action of a variety of cellular interactions and secreted factors such as transforming growth factor-β (TGF-β). In the Journal of Clinical Investigation, Nishimura and co-workers pinpoint lung fibroblasts as key participants in lung inflammation and COPD. In a model of COPD induced by interleukin 1β (IL-1β), they observe that IL-1β results in higher expression of the integrin αvβ8 on the surface of lung interstitial fibroblasts. This integrin is required for cleavage and activation of TGF-β. Active TGF-β then binds to its receptor on fibroblasts in an autocrine or paracrine way, which results in release of the chemokines CCL2 and CCL20. Both of these chemokines can recruit dendritic cells (DCs) to lung-draining lymph nodes, where they prime T cell responses. Although not formally demonstrated, lung epithelial damage, such as by smoke particulates, may trigger IL-1b release and act as an initiating factor. Fibroblasts therefore seem to have a central role in COPD and potentially other forms of pathological lung inflammation.

J. Clin. Invest. 121, 2863–2875 (2011)