RT Journal Article
SR Electronic
T1 Pulmonary macrophage subsets associated with lung allograft dysfunction revealed by single-cell RNA sequencing
JF ERJ Open Research
JO erjor
FD European Respiratory Society
SP 201
DO 10.1183/23120541.LSC-2022.201
VO 8
IS suppl 8
A1 Sajad Moshkelgosha
A1 Allen Duong
A1 Gavin Wilson
A1 Tallulah Andrews
A1 Benjamin Renaud-Picard
A1 Gregory Berra
A1 Shaf Keshavjee,
A1 Sonya Macparland
A1 Jonathan Yeung
A1 Tereza Martinu
A1 Stephen Juvet
YR 2022
UL http://openres.ersjournals.com/content/8/suppl_8/201.abstract
AB Lung transplant (LT) recipients experience a low survival rate due to chronic lung allograft dysfunction (CLAD). Acute lung allograft dysfunction (ALAD) is a risk factor for CLAD. The contribution of lung macrophages (Macs) to ALAD and CLAD is not clear.Determine the role of Macs in dysfunctional lung allografts using single-cell RNA sequencing (scRNAseq) during quiescence, ALAD, and CLAD.Fresh BAL cells from 6 LT patients - 3 stable and 3 ALAD - and cells from 4 explanted CLAD lungs underwent scRNAseq. R Bioconductor and Seurat were used to perform QC, annotation, and pathway analysis. Donor and recipient deconvolution was performed using single nucleotide variations.We identified two Mac subsets uniquely present in ALAD compared to stable BAL (Fig 1A). Using pathway analysis, we annotated these as pro-inflammatory interferon-stimulated gene (ISG) and metallothionein-mediated inflammatory (MT) Macs. Using publicly available BAL scRNAseq datasets, we found that ISG and MT Macs are associated with severe inflammation in COVID-19 patients (Fig 1B). Analysis of cells from CLAD lungs revealed similar Mac populations (Fig 1C). Deconvolution demonstrated that donor-derived Macs are lost with time post-transplant (Fig 1D).Using scRNAseq, we identified specific Macs that may be associated with allograft dysfunction, raising the possibility that these cells may represent important therapeutic targets. FootnotesCite this article as ERJ Open Research 2022; 8: Suppl. 8, 201.This article was presented at the 2022 ERS Lung Science Conference, in session “Poster Session 2”.This is an ERS Lung Science Conference abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).