Early immune signatures of copd: linking inflammation to disease progression

The National Heart, Lung, and Blood Institute awarded Brigham & Women's Hospital Inc. $120,825 on April 1, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to investigate early immune signatures in chronic obstructive pulmonary disease and their relationship to disease progression.

The research builds on prior K08-funded work examining hedgehog interacting protein deficiency and lymphocytic inflammation in COPD. The recipient will focus on a specific CD8+ T cell subset expanded in mild to moderate COPD, using longitudinal cohorts and single-cell immune profiling to determine whether this subset is associated with COPD development and progression, and to identify the clonal and antigenic drivers underlying its expansion. The work emphasizes defining the transcriptomic, clonal, and antigenic properties of this CD8+ T cell subset to advance understanding of inflammatory pathogenesis and potentially inform novel therapeutic strategies to slow disease progression.

Performance occurs in Boston, Massachusetts, with a completion date of December 31, 2027. The award is a Project Grant, classified as assistance funding. Brigham & Women's Hospital operates as a subsidiary of Partners Healthcare System Incorporated and maintains substantial research activity with NIH institutes, particularly NHLBI.

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.