Inflammatory pathways are involved in orchestrating various tissue responses in chronic obstructive pulmonary disease (COPD), with emerging evidence supporting a potential role of dysregulated immunity in the development or progression of the disease. The immune regulatory influences that control the inflammatory response in COPD remains poorly defined. Regulatory T (Treg) cells appear to have a central role in controlling the autoimmune response and allergic airway disease. The focus of this project is to investigate the role of Treg in the pathobiology of COPD. In view of the exaggerated T cell inflammatory response in COPD, my hypothesis is that Treg cells are impaired in patients with COPD, and the weak Treg activity in these individuals contributes to the pathogenesis of this disease.
The aims of this project will be 1) to quantitate the lung tissue Treg cell response in subjects with COPD and controls, and compare it with that obtained from blood and bronchoalveolar fluid (BAL). Flow cytometry will be used for quantitation of Treg cells from lung tissue, blood, and BAL;2) to determine Treg cell function exvivo from subjects with COPD and matched controls (smokers and nonsmokers), by isolating CD4+CD25hi cells from the peripheral blood of subjects and performing conventional CD4+CD25- and CD8+ proliferative and cytokine production assays;3) to determine the effect of smoking on Treg cell function obtained from peripheral blood of subjects with COPD and controls by performing the proliferative and cytokine assays with and without cigarette smoke extract. Identifying a substantial role of Treg cells in COPD will advance the understanding of factors involved in COPD development and progression, and could lead to novel therapeutic approaches by manipulating Treg cells. Establishing the effects of smoking on Treg cells could also lead to potential prevention strategies by Treg cell manipulation. Both the reseach and the patient care missions of the Temple Universtiy School of Medicine will be served greatly by this project. In addition, one of my main objectives is to become an independent translational researcher. Implementing the proposed work in the laboratories of experts in the fields of immunology, flow cytometry, and other relevant basic science techniques, and participating in a structured educational program enhance the education mission of the institution.
|Chatila, W M; Criner, G J; Hancock, W W et al. (2014) Blunted expression of miR-199a-5p in regulatory T cells of patients with chronic obstructive pulmonary disease compared to unaffected smokers. Clin Exp Immunol 177:341-52|