An Epithelial Integrin Regulates the Amplitude of Protective Lung Interferon Responses against Multiple Respiratory Pathogens

Meliopoulos, Victoria A.; Van de Velde, Lee-Ann; Van de Velde, Nicholas C.; Karlsson, Erik A.; Neale, Geoff; Vogel, Peter; Guy, Cliff; Sharma, Shalini; Duan, Susu; Surman, Sherri L.; Jones, Bart G.; Johnson, Michael D. L.; Bosio, Catharine; Jolly, Lisa; Jenkins, R. Gisli; Hurwitz, Julia L.; Rosch, Jason W.; Sheppard, Dean; Thomas, Paul G.; Murray, Peter J.; Schultz-Cherry, Stacey

Integrins are heterodimers composed of α and β subunits that regulate a plethora of cellular functions including cell-matrix and cell-cell adhesion, cell activation, and the recognition and post-translational processing of molecules [8] . In the lung microenvironment, β6 (encoded by Itgb6) exclusively pairs with the αV subunit and expression of the αVβ6 heterodimer is limited to epithelial cells. In this context, αVβ6 plays a key role in controlling several steps in lung homeostasis. Mice lacking the β6 subunit (β6 KO) have highlighted the central role αVβ6 integrin plays in balancing the pulmonary environment during injury [9, 10] . For example, in both bleomycin-induced and PAR1-mediated ventilator-associated lung injury and airway hyper-responsiveness models, β6 KO mice were protected from ALI [11] [12] [13] . β6 KO mice also had reduced IL-1β-mediated lung injury in a model of bronchopulmonary dysplasia due to decreased inflammation and cellular infiltrate to the lung [14] . Alveolar macrophages isolated from β6 KO are characterized as large and foamy and express high amounts of MMP12 [15, 16] .