Multiplatform Single-Cell Analysis Identifies Immune Cell Types Enhanced in Pulmonary Fibrosis

Ana P.M. Serezani, Bruno D. Pascoalino, Julia M.R. Bazzano, Katherine N. Vowell, Harikrishna Tanjore, Chase J. Taylor, Carla L. Calvi, A. Scott McCall, Matthew D. Bacchetta, Ciara M. Shaver, Lorraine B. Ware, Margaret L. Salisbury, Nicholas E. Banovich, Peggy L. Kendall, Jonathan A. Kropski, Timothy S. Blackwell

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Immune cells have been implicated in idiopathic pulmonary fibrosis (IPF), but the phenotypes and effector mechanisms of these cells remain incompletely characterized. We performed mass cytometry to quantify immune cell subsets in lungs of 12 patients with IPF and 15 organ donors without chronic lung disease and used existing single-cell RNA-sequencing data to investigate transcriptional profiles of immune cells overrepresented in IPF. Among myeloid cells, we found increased numbers of alveolar macrophages (AMØs) and dendritic cells (DCs) in IPF, as well as a subset of monocyte-derived DCs. In contrast, monocyte-like cells and interstitial macrophages were reduced in IPF. Transcriptomic profiling identified an enrichment for IFN-γ response pathways in AMØs and DCs from IPF, as well as antigen processing in DCs and phagocytosis in AMØs. Among T cells, we identified three subsets of memory T cells that were increased in IPF, including CD41 and CD81 resident memory T cells (TRM) and CD81 effector memory cells. The response to the IFN-γ pathway was enriched in CD4 TRM and CD8 TRM cells in IPF, together with T cell activation and immune response-regulating signaling pathways. Increased AMØs, DCs, and memory T cells were present in IPF lungs compared with control subjects. In IPF, these cells possess an activation profile indicating increased IFN-γ signaling and upregulation of adaptive immunity in the lungs. Together, these studies highlight critical features of the immunopathogenesis of IPF.

Original languageEnglish
Pages (from-to)50-60
Number of pages11
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume67
Issue number1
DOIs
StatePublished - Jul 2022

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