Fig. 1: TLR7 is increased in human and experimental COPD.

a TLR7 mRNA levels in airway epithelial brushings from non-smokers (NS), healthy smokers without COPD (Smoker) and COPD patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I (mild) or II (moderate) disease (n = 12 NS; n = 12 Smokers; n = 15 mild or moderate COPD). b TLR7 mRNA levels in lung parenchyma cores from NS and COPD patients with GOLD stage IV (severe) disease (n = 16 NS; n = 48 severe COPD). Differential gene expression analysis was performed using published microarray datasets (GEO accession numbers GSE5058 and GSE27597) and the numbers in panels a and b represent the false discovery rate (FDR), whereby *denotes FDR of COPD vs. NS; and ^# denotes FDR of COPD vs. Smoker. The data are presented as box and whiskers with min to max showing all points. c Correlation analysis of anti-Smith antibody levels in serum and forced expiratory volume in 1 second (FEV₁) of mild-to-moderate COPD patients (n = 40). d Human lung sections stained with tryptase, TLR7 and DAPI by immunofluorescence, and e TLR7⁺ mast cells were enumerated in sections from NS controls (n = 4), smoker (n = 6) and COPD patients (n = 11). The numbers of TLR7⁺ mast cells correlated with f FEV₁% predicted, g pack years of cigarettes, and h low attenuation areas less than a threshold of −950 Hounsfield units (%LAA950) in NS, smoker, and COPD patients. i Induction of experimental COPD where wild-type (WT) BALB/c mice (female, 6–8 weeks old) were exposed to nose-only inhalation of cigarette smoke (CS) for up to 12 weeks, controls received normal air. j Tlr7 mRNA levels in whole lungs of WT mice exposed to normal air or CS after 4, 6, 8, and 12 weeks (n = 6 mice per group). Tlr7 mRNA levels in blunt-dissected k airways and l lung parenchyma after 8 weeks of CS exposure (n = 6 mice per group). Wild-type (WT) BALB/c mice (n = 6) were exposed to CS for 8 weeks to induce experimental COPD, controls were exposed to normal air. m TLR7 protein was assessed in mouse lungs by immunoblot, and n quantitated by densitometry analysis of fold change normalised to β-actin (n = 6 mice per group). o Representative micrographs (n = 3 mice per group) of TLR7 immunostaining in small airways (top) and lung parenchyma (bottom) of WT mice exposed to normal air (left) or CS (right) for 8 weeks. Scale bars, 50 µm. WT BALB/c mice were exposed to 8 weeks of CS, control mice breathed normal air. p Total TLR7⁺ cells, q mMCP4⁺TLR7⁺ mast cells and r F4/80⁺TLR7⁺ macrophages enumerated in whole lung sections (n = 6 mice per group). All data are presented as means ± s.e.m. and are representative of two independent experiments. For panel c, f–h, correlation analyzes were performed using Spearman’s rank correlation coefficient test. For panel e, compared to NS or smokers using one-way ANOVA with Bonferroni’s multiple comparison test. The rest of the panels compared COPD to normal air-exposed controls using a two-tailed Mann–Whitney test. Source data are provided as a Source Data file.