Profibrotic monocyte-derived alveolar macrophages as a biomarker and therapeutic target in systemic sclerosis-associated interstitial lung disease

Interstitial lung disease (ILD) is present in over 60% of patients with systemic sclerosis (SSc) and is the leading cause of SSc-related deaths. Profibrotic monocyte-derived alveolar macrophages (MoAM) play a causal role in the pathogenesis of pulmonary fibrosis in animal models where their persistence in the niche requires signaling through the Colony Stimulating Factor 1 Receptor (CSF1R). We hypothesized that the presence and proportion of MoAM in bronchoalveolar lavage (BAL) fluid from patients with SSc-ILD may be a biomarker of ILD severity. We performed spatial transcriptomics to localize profibrotic MoAM to the alveolar space and identified expansion of interstitial macrophages spilling into the alveolar space. Our findings suggest that the proportion of profibrotic MoAM and interstitial macrophages in BAL fluid may serve as a biomarker of SSc-ILD and credential them as possible targets for therapy. 6 donor and 5 SSc lung tissue sections were obtained. An approximately 10x10x10 mm piece of lung tissue was cut, fixed, and mounted to one of two Xenium slides for each section. Due to the instrument malfunction, the first run (samples with “:1” suffix) was aborted mid-run, and slides were left on the instrument for ~48 hours. The slides were recovered, stored at 4 °C for an additional 24 hours, and then the run was successfully repeated using a new set of reagents. To assess the impact of technical issues on the data quality, we have prepared additional sections from the same tissue blocks (samples with “:2” suffix) and analyzed them using the same gene panel and tissue segmentation kit (replacement reagents were kindly provided by 10x Genomics). The second run completed without technical issues.