TLR7 promotes smoke-induced lung damage through the activity of mast cell tryptase

Abstract Toll-like receptor (TLR)7 is known for eliciting immunity against single-stranded RNA viruses. TLR7 was increased in both human and cigarette smoke (CS)-induced experimental chronic obstructive pulmonary disease (COPD). Severity of CS-induced emphysema and COPD was reduced in TLR7-deficient mice whilst inhalation of imiquimod (TLR7-agonist) induced emphysema in naïve mice. Imiquimod-induced emphysema was reduced in mice treated with mast cell stabilizer cromolyn or deficient in mast cell protease-6. Therapeutic treatment with anti-TLR7 monoclonal antibody suppressed CS-induced emphysema, experimental COPD and accumulation of pulmonary mast cells. We demonstrate an unexpected role for TLR7 in mediating emphysema and COPD through mast cell activity.