Restoring regulatory T cells in cigarette smoke-induced emphysema – UROP Spring Symposium 2021

Restoring regulatory T cells in cigarette smoke-induced emphysema

Danny Jandali


Research Mentor(s): Christine Freeman, Research Associate Professor
Research Mentor School/College/Department: Internal Medicine, Michigan Medicine
Presentation Date: Thursday, April 22, 2021
Session: Session 5 (3pm-3:50pm)
Breakout Room: Room 11
Presenter: 6

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Our research seeks to develop novel therapies to prevent chronic obstructive pulmonary disease progression (COPD), and associated mortality, through the demonstration that regulatory T cells, otherwise known as Tregs, reduce lung injury in a murine cigarette smoke exposure model. We hypothesize that by restoring regulatory T cells in subjects with COPD, natural killer cell (NK) cytotoxicity (percentage of cell death that occurs over the baseline) will be inhibited, therefore reducing the impact of natural killer cells on lung damage. Presently, our studies show that natural killer cell cytotoxicity positively correlates with epithelial cell apoptosis, indicating their relationship with tissue pathology. Additionally, we have shown that regulatory T cells are diminished in COPD, and that murine Tregs suppress NK cytotoxicity in vitro and in vivo following adoptive transfer. To further our murine exposure model, we utilize a Jaeger-Baumgartner Smoking Machine to expose the subjects to cigarette smoke for one hour per day for five days of the week to emulate the NK cytotoxicity observed in COPD subjects. These exposed mice will then be transferred nTreg, eTreg, mTreg, and Tconv or vehicle (negative controls) to later be euthanized and evaluated for Treg suppression of NKs, Treg phenotype stability, Treg migration and measurements of lung injury/inflammation, Treg suppression of T cell cytokine production, and Treg transcriptional signatures.Through sequencing, data processing and cell-type identification, power calculation and statistical analysis, and bioinformatic analysis for scRNA-sequences, we anticipate suppression of NK cytotoxicity with the transfer of mTregs, although we do expect for this suppression to decrease following sustained CS exposure. We also expect positive correlation between the stability of the Treg phenotype and the ability to inhibit natural killer cells.

Authors: Danny Jandali
Research Method: Laboratory Research

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