Chronic Obstructive Pulmonary Disease and Cigarette Smoke Lead to Dysregulated Mucosal-associated Invariant T-Cell Activation

Megan E. Huber, Emily Larson, Taylor N. Lust, Chelsea M. Heisler, Melanie J. Harriff

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic obstructive pulmonary disease (COPD) is associated with airway inflammation, increased infiltration by CD8+ T lymphocytes, and infection-driven exacerbations. Although cigarette smoke is the leading risk factor for COPD, the mechanisms driving the development of COPD in only a subset of smokers are incompletely understood. Lung-resident mucosal-associated invariant T (MAIT) cells play a role in microbial infections and inflammatory diseases. The role of MAIT cells in COPD pathology is unknown. Here, we examined MAIT cell activation in response to cigarette smoke-exposed primary human bronchial epithelial cells (BECs) from healthy, COPD, or smoker donors. We observed significantly higher baseline MAIT cell responses to COPD BECs than healthy BECs. However, infected COPD BECs stimulated a smaller fold increase in MAIT cell response despite increased microbial infection. For all donor groups, cigarette smoke-exposed BECs elicited reduced MAIT cell responses; conversely, cigarette smoke exposure increased ligand-mediated MR1 surface translocation in healthy and COPD BECs. Our data demonstrate that MAIT cell activation is dysregulated in the context of cigarette smoke and COPD. MAIT cells could contribute to cigarette smoke- and COPD-associated inflammation through inappropriate activation and reduced early recognition of bacterial infection, contributing to microbial persistence and COPD exacerbations.

Original languageEnglish (US)
Pages (from-to)90-102
Number of pages13
JournalAmerican journal of respiratory cell and molecular biology
Volume68
Issue number1
DOIs
StatePublished - Jan 1 2023

Keywords

  • chronic obstructive pulmonary disease
  • cigarette smoke
  • MAIT cells
  • MR1
  • Streptococcus pneumoniae

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Fingerprint

Dive into the research topics of 'Chronic Obstructive Pulmonary Disease and Cigarette Smoke Lead to Dysregulated Mucosal-associated Invariant T-Cell Activation'. Together they form a unique fingerprint.

Cite this