Transcriptional and spatial profiling of T-Cell subsets in progressive pulmonary fibrosis 3627

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Abstract Description Idiopathic pulmonary fibrosis (IPF) is a severe condition that can lead to respiratory failure. T-cells are increased in IPF compared to non-diseased control lungs, but the contribution of T-cell subsets in pulmonary fibrosis (PF) remains unclear. We obtained lungs from IPF (n = 9), autoimmune-associated pulmonary fibrosis (n = 10), and non-fibrotic control (n = 10) declined during transplant surgery. We used co-detection by indexing (CODEX) and QuPath to identify cells in tissue microarray sections from paraffin-embedded controls and IPF lung samples. Single-cell RNA sequencing (scRNA-seq) was performed on whole lung-isolated cells, and Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) on CD3-isolated T lymphocytes from the same subjects and autoimmune-associated pulmonary fibrosis patients. We identified CD4 T-cells, regulatory T-cells, CD8 T-cells, and B-cells by CODEX around the epithelium in IPF lungs. HLA-DR levels were higher in IPF epithelial cells than in controls; and a pseudobulk analysis (DEseq2) showed that transitional alveolar type 2 (AT2) cells have elevated MHC II regulatory factors in IPF than controls or autoimmune PF. Among eleven subsets of T-cells identified by CITE-seq, several IPF T-cells showed regulation of epidermal growth factor receptor (EGFR), while Jak-STAT activities dominated autoimmune PF T-cells. Thus, IPF T-cell activities are distinct from other forms of PF and might be influenced by unconventional responses. Funding Sources (Support: K12AR084232, P01HL172729) Topic Categories Immune Mechanisms of Human Disease (HUM)

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