Journal Article

Single‐Cell RNA Sequencing of Human Lung Tissues Reveals Metallothionein‐Positive T Cells as a Novel Potential Marker of Susceptibility to Chronic Obstructive Pulmonary Disease

Sun, Ying, Chen, Yahong, Lv, Jialu, Zhang, Muzhi, Wang, Jiajia, Wang, Wei, Lv, Zhe, Feng, Zhihong, Shi, Fanyu, Liu, Yang, Liu, Zengqing, Chen, Yan, Liu, Jie, Mu, Mi, Long, Huanyu, Chen, Chen, Cui, Ye, Corrigan, Chris J., Xu, Mengyu, Ren, Xiaoxia, Zhang, Ruoyang, Deng, Hui, Wang, Zengtao, Fan, Yang

2026

Overview

Chronic obstructive pulmonary disease (COPD) is a highly heterogeneous disease with complex pathogenesis. Identifying high‐risk populations and implementing timely prevention strategies are critical to reducing the disease burden. Single‐cell RNA sequencing of lung tissue from control never‐smokers, patients with pre‐COPD, and COPD patients revealed a novel T cell subset characterized by high expression of metallothionein (MT) genes, designated MT‐high T cells. These cells were progressively depleted in the lungs with disease progression. A similar decline was observed in the peripheral blood using flow cytometry, highlighting the potential of these cells to serve as an accessible biomarker of disease progression. Functional analysis indicated that MT‐high T cells suppress CD8+ T cell cytotoxic activity, suggesting a key immunoregulatory role in disease pathogenesis. Receiver operating characteristic curve analysis demonstrated the excellent potential of MT‐high T cell frequency to predict susceptibility to COPD. These findings establish MT‐high T cells as promising biomarkers for identifying individuals at risk for COPD and as novel targets for future therapeutic and prophylactic strategies. Using single‐cell RNA sequencing of lung samples and flow cytometry of peripheral blood, we identified a novel T cell subset with high metallothionein (MT) expression. These MT‐high T cells suppress CD8+ T cell cytotoxicity and are progressively depleted from healthy controls to chronic obstructive pulmonary disease (COPD) patients, positioning them as early biomarkers for COPD risk and key regulators of disease pathogenesis.

• Publisher: John Wiley & Sons, Inc,Wiley
• Subject: Aged / biomarker / Biomarkers / Biomarkers - metabolism / Cells / Chronic obstructive pulmonary disease / Female / Flow cytometry / Health care / Humans / Hypotheses / Lung - metabolism / Lymphocytes / Male / Metallothionein - genetics / Metallothionein - metabolism / Middle Aged / Patients / Pulmonary Disease, Chronic Obstructive - genetics / Pulmonary Disease, Chronic Obstructive - immunology / Pulmonary Disease, Chronic Obstructive - metabolism / Sequence Analysis, RNA - methods / Single-Cell Analysis - methods / Single-Cell Gene Expression Analysis / single‐cell RNA sequence analysis / T Cells / T-Lymphocytes - metabolism