IL-15-Mediated IL-6Ra Effector Memory CD8+ T Cells in Dysfunctional Lung Responses During Cigarette Smoke Exposure and Influenza Viral Infections
Abstract
Our proposal focuses on the interface of IL-15 and IL-6R effector memory CD8+ T cells as a significant contributor in thedevelopment of pathological hyperinflammatory and fibrotic responses in the smokers and COPD subjects during influenzainfection. The goal of the studies is to characterize the IL-15 regulatory pathways in the lung that are induced by CS and influenzavirus and the mechanisms by which IL-15 mediates induction of these pathways that contribute to the AECOPD and fibroticphenotype of COPD and CS-related lung diseases. We will test the hypothesis this using a series of mouse and human studies. InAim 1, we propose to determine the importance of IL-15 in regulating macrophage and fibroblast function and their contribution tolung inflammation, injury and fibrotic responses during CS exposure + Flu infection mouse model. In Aim 2, we will determine themolecular and cellular mechanisms by which IL-15 modulates IL-6Rhigh EM CD8+ T cells and its contribution to lung injury andfibrotic responses during CS + Flu. Lastly in Aim 3, we will study the clinical implication of a novel IL-6Rhigh EM CD8+ T cellsubset with the capacity to produce type II cytokines smokers and in patients with COPD.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2020
- Accession Number
- AD1118340
Entities
People
- Charles S Dela Cruz
Organizations
- Yale University