Early Immune Signatures of COPD: Linking Inflammation to Disease Progression

/ABSTRACT The R03 application builds upon Dr. Yun’s K08-funded study, which investigated how hedgehog interacting protein (HHIP) deficiency contributes to lymphocytic inflammation in chronic obstructive pulmonary disease (COPD). Through that work, we identified unique CD8+T cell populations in both a murine model and human COPD lungs. In this proposal we will focus on a specific CD8+T cell subset expanded in mild to moderate (early) COPD and investigate its contribution to COPD development and progression. By leveraging longitudinal cohorts and single-cell immune profiling, we will determine 1) whether this subset is associated with COPD development and progression, and 2) the clonal and antigenic drivers that underlying its expansion. Our emphasis on defining the transcriptomic, clonal, and antigenic properties of this CD8+T cell subset in COPD will advance our understanding of inflammatory pathogenesis and potentially provide a foundation for novel therapeutic strategies aimed at slowing disease progression. Project Number: 1R03HL183108-01 | Fiscal Year: 2026 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Jeong Yun | Institution: BRIGHAM AND WOMEN'S HOSPITAL, BOSTON, MA | Award Amount: $120,825 | Activity Code: R03 | Study Section: Special Emphasis Panel[ZRG1 RCCS-P (92)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R03HL18310801