KLRG1+ TEMRA CD8+ T cells are enriched in single-cell analysis of mild-moderate COPD lung

Rationale: Despite the importance of inflammation chronic obstructive pulmonary disease (COPD), inflammation in lung tissue from patients with mild-moderate COPD has not been well described at the molecular and single-cell level.

Objectives: We apply a multi-omic, single-cell approach to define inflammation in lung tissue from patients with mild-moderate COPD.

Methods: We performed single-cell transcriptomics (RNA-seq) and proteomics (CITE-seq) on lung tissue from patients with mild-moderate COPD (n=5, GOLD I/II) compared to control (n=5), emphysema without airflow obstruction (n=5), and “end-stage” COPD lung explants. We examine enriched cell clusters and their interactome. We integrated our dataset with public scRNA-seq datasets of explanted COPD lung and a murine model of COPD driven by Hhip(+/-). We validated our findings in a lung bulk RNA-seq dataset from an independent patient cohort (N=316).

Measurements and Main Results: Mild-moderate COPD lungs are enriched in two CD8+ T cell populations: 1)KLRG1+ TEMRA cells expressing cytotoxicity, TIGIT, and CX3CR1; and 2)T resident memory (TRM) cells expressing long-term memory, PD-1, TACTILE, and CCR5. These CD8+ T cell subsets interact with monocytes via IFNG, TNFA, and ANXA1-FPR1 axes. In an independent cohort, the gene signature for CD8+ KLRG1+ TEMRA cells is increased in GOLD I/II COPD compared to control or GOLD III/IV patients. In cross-species comparison, these cells resemble CD8+ KLRG1+ T cells implicated in experimental COPD.

Conclusions: CD8+ KLRG1+ TEMRA and TRM cells are increased in mild-moderate COPD lung and may contribute to inflammation that precedes severe disease.