Bitterlich, Laura M. (2025) Investigating MSC Immunomodulation in the Obese Microenvironment. PhD thesis, National University of Ireland Maynooth.
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Laura Bitterlich PhD Thesis.pdf
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Abstract
The proportion of people living with obesity is constantly on the rise, which makes it an important factor to consider in any clinical setting. The obese microenvironment introduces a range of pro-inflammatory factors and other molecules that can affect immune cells and treatments. Mesenchymal stromal cells (MSCs) are a valuable asset for the treatment of inflammatory conditions due to their immunomodulatory and their tissue regenerative abilities. MSCs are able to communicate with surrounding immune cells and respond to signals from the microenvironment. However, this makes MSCs vulnerable to perturbations in that microenvironment. This thesis investigates how certain prominent factors from the obese microenvironment, the free fatty acids oleate and palmitate and the adipokine leptin, affect MSC phenotype and function. Differences between T cell suppression and macrophage suppression by palmitate exposed MSCs were discovered, and the underlying mechanism for how palmitate affects macrophage suppression by MSCs was further elucidated. In addition to the direct effects of these factors on MSCs, we were also interested in the concept of innate immune training of macrophages by factors elevated in the obese microenvironment, and how MSCs might be able to interfere with this training. Innate immune training can lead to a hyperinflammatory activation of macrophages, which, while protective in many cases of infectious disease, has the potential to result in a more severe outcome of chronic autoimmune disease. MSCs, which are powerful suppressors of macrophage inflammation, have already been shown to suppress house dust mite-mediated training in our lab. Building on this research, a training protocol was established and pathways through which MSCs may be inhibiting training were investigated. Overall, this research revealed avenues to be explored in MSC-macrophage interactions, highlighting the potential for the use of MSCs in patients with inflammatory conditions who are living with obesity, and identifying pathways through which innate immune training could be controlled.
Item Type: | Thesis (PhD) |
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Keywords: | MSC Immunomodulation; Obese Microenvironment; |
Academic Unit: | Faculty of Science and Engineering > Biology |
Item ID: | 19953 |
Depositing User: | IR eTheses |
Date Deposited: | 06 Jun 2025 14:47 |
URI: | https://mural.maynoothuniversity.ie/id/eprint/19953 |
Use Licence: | This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here |
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