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Master Thesis in Research Group “Immunopathology of COPD” at the Institute of Lung Biology and Diseases, Helmholtz Zentrum München

"The role of T-cell subsets and pro-inflammatory mediators in the pathogenesis of chronic obstructive pulmonary disease"

06.09.2021

Chronic obstructive pulmonary disease (COPD) is defined as a chronic inflammatory disorder characterized by progressive airflow limitation and is composed of emphysema and chronic bronchitis. Inflammation, which may be caused by environmental exposures like cigarette smoke or pollution, is a main pathogenic factor in the development of COPD (Conlon et al. 2020, Nature). In response to pulmonary inflammation, leukocytes both innate and adaptive cells infiltrate the lung and contribute to the pathophysiology of COPD. One important mediator of adaptive immunity is T-lymphocytes. T lymphocytes get activated and differentiate into multiple subsets which may cause lung tissue destruction either by direct cytolytic activities or through the secretion of pro-inflammatory mediators that recruits and activates other immune cell types. In support, both CD4+ T helper cells and CD8+ cytotoxic T cells were found to be increased in the lungs of COPD patients. CD4+ T cells can differentiate into Th1, Th2, Th17, Treg as well as Tfh cells under certain inflammatory conditions and the specific contribution of these subsets to COPD pathogenesis are still under investigation.

What will you be working on?

Adaptive immune reactions are involved in the pathogenesis of COPD, in particular, inflammation and immunity mediated by T cells has been identified as a key component. Moreover, abnormalities in the number and function of CD4+ T cell subsets, including Th1, Th2, Th17, Treg and Tfh cells in the lungs of COPD patients has an effect on chronic inflammation and perpetuation of disease pathogenesis. In light of these previous findings, the aim of this project is to investigate the involvement of T helper cells in particular Tregs and Tfh cells in the pathogenesis of COPD. The molecular mechanisms underlying how they contribute to disease development and which factors are regulating their differentiation will be identified.

What techniques will you use?

This project will focus mainly on T-lymphocytes and require in vitro cell culture assays of primary T cells. You will learn how to isolate primary T cells from mouse and how to maintain them in vitro. Moreover, T cell differentiation into Th1, Th2, Th17, Treg as well as Tfh subsets will be performed in vitro. Conventional molecular biological methods (Western blotting, qPCR, immunohistochemistry staining) will be performed frequently. Moreover, more specialized methods (Flow Cytometry analysis of intracellular and surface stainings and fluorescence microscopy) will be also utilized. This project offers a possibility to learn more about T cell biology and their contribution into disease pathogenesis.

Contact Persons
Dr. Yildirim: oender.yildirim@helmholtz-muenchen.de
Dr. Conlon: thomas.conlon@helmholtz-muenchen.de