Dissecting the immune cell niche in pulmonary sarcoidosis – CXCL10+ monocyte-derived macrophages are potential drivers of TH17.1 inflammation

<fig><object-id>erj;64/suppl_68/OA953/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig> <bold>Background/Objectives:</bold> This study aims to explore the immune landscape of pulmonary sarcoidosis at single-cell level to enhance our understanding of the development, role and impact of TH17.1 inflammation, repeatedly observed in BAL and affected tissues. <bold>Methods:</bold> We examined BAL fluid from 16 sarcoidosis patients and 10 control individuals using single-cell RNA sequencing (scRNAseq), ELISA and flow cytometry with and without prior stimulation. <bold>Results:</bold> Transcriptional profiling of approximately 85,000 native BAL cells revealed a notable expansion of myeloid cells expressing CXCL10 and CCL2 in sarcoidosis patients together with increased GM-CSF levels. At the T-cell level, a moderate TH17.1 signature was present in native cells, with further inducibility upon stimulation. In contrast, TH cells in the control group displayed only an inducible TH1 signature. Flow cytometry validation analyses demonstrated an increase in TH17.1 cell populations in the sarcoidosis group upon stimulation. Analysis of potential ligand-receptor pairs between myeloid and TH17.1 cells suggested an enhanced interaction through multiple upregulated chemokine signaling pathways. <bold>Discussion:</bold> Our findings confirm the presence of a proinflammatory TH17.1 cell population in the BAL of sarcoidosis patients, while emergence of CXCL10+ macrophages may contribute to generation and activation of TH17.1 cells.