Journal club with Gisli Jenkins from 21/9/15
Written by David Salman, Richard Toshner and Joana Alçada
Edited by Sarah Allden
We recently welcomed Dr Gisli Jenkins, Clinical Associate Professor & Reader in Pulmonary Biology from the University of Nottingham to the IRD Journal Club.
His recent publication “Influenza Promotes Collagen Deposition via αvβ6 Integrin-mediated Transforming Growth Factor β Activation” served as a starting point to discuss various aspects of research in lung fibrosis. The paper explores the relationship between influenza and idiopathic pulmonary fibrosis via transforming growth factor β (TGF-β), a cytokine involved in development, inflammation and wound repair.
The authors hypothesised that influenza-induced epithelial cell damage would stimulate toll-like receptor 3 (TLR3) activity, a receptor that recognizes by-products from viruses such as influenza. This in turn may lead to activation of an epithelial specific cell surface molecule called integrin αvβ6, which would then turn on TGF-β signalling.
The results first indicate that influenza virus activates TGF-β in airway epithelial cells. Secondly, mutation of the epithelial cells with a non-functioning TLR3 protein inhibited this response, suggesting that the process is mediated through TLR3 signalling. Finally, blocking integrin αvβ6 with an antibody reduced influenza-induced epithelial cell death. Influenza was also shown to increase deposition of matrix materials, which are correlated with pulmonary fibrosis, throughout the lungs of infected mice. In addition, levels of integrin αvβ6 expression were increased in those mice. Conversely, blocking the expression of this integrin with antibody inhibited the development of a fibrosis-like picture in the lungs. Therefore, the Jenkins group have elegantly demonstrated a link between influenza infection and the mechanisms of pulmonary fibrosis development, through integrin αvβ6-mediated TGF- β and TLR3 signalling.
The discussion Dr Jenkins kindly participated in was a wide ranging one, touching upon not just his own group’s research record, but also a more global view of translational research, with particular reference to idiopathic pulmonary fibrosis. He touched upon some of the molecules currently at the phase 2 trial stage for IPF, such as anti IL-13 and anti IL-4, as well as his thoughts upon the possible future directions that research in this area will take.
See Dr Jenkins’ full paper here http://www.jbc.org/content/289/51/35246.long