Pisarska, Marta M.
(2021)
Characterisation of Mucosal Associated
Invariant T cells function and
metabolism in health and obesity.
PhD thesis, National University of Ireland Maynooth.
Abstract
Obesity has developed into a worldwide pandemic, affecting individuals
regardless of their socio-economic status, gender or age. It is associated with
development of multiple co-morbidities including type 2 diabetes mellitus, which
have been shown to be underpinned by inflammation. Indeed, excessive
adiposity has been shown to be associated with a large dysregulation of immune
cell function, including altered phenotype of mucosal-associated invariant T
(MAIT) cells. MAIT cells from people with obesity were shown to have enhanced
IL-17 production, accompanied by impaired IFNγ expression. As of now, very little
is known about the control of MAIT cell function, therefore more research is
required to understand their biology in order to identify the altered process, which
leads to their dysfunction in obesity. Immunometabolism of MAIT cells became
the focus of this thesis as previous data indicated it as a key biological process
that controls immune cell function. Here we confirmed previously published data,
showing that MAIT cells are potent producers of IFNγ and IL-17 cytokines and
that MAIT cells can proliferate and expand upon stimulation. In addition, we
reported that MAIT cells enhance glycolysis upon activation, which in turn is
controlled by the influx of amino acids into the cells via LAT1 amino acid
transporters. Glycolytic metabolism was required for successful IFNγ production
as well as proliferation and expansion of MAIT cells. People with obesity have
impaired IFNγ expression and MAIT cell expansion that was accompanied by
impaired glycolytic metabolism. Collectively our data indicates that MAIT cells
effector functions are in part controlled by the intrinsic metabolic pathways
including the glycolytic metabolism. Defect in glycolysis or glycolysis-associated
pathways as observed in obesity, leads to their dysfunction and altered immune
cells responses.
Item Type: |
Thesis
(PhD)
|
Keywords: |
Mucosal; Invariant T cells function; metabolism; health; obesity; |
Academic Unit: |
Faculty of Science and Engineering > Biology |
Item ID: |
14935 |
Depositing User: |
IR eTheses
|
Date Deposited: |
19 Oct 2021 11:23 |
URI: |
|
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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