Endocrine Abstracts

Introduction: MAIT cells are a unique subset of T-cells, that have been conserved throughout 150 million years of mammalian evolution. They can contribute to rapid pathogen control, tissue repair and anti-cancer immunity, but can also cause inflammation and tissue damage in diseased settings. Previously, we have reported dysregulated peripheral blood MAIT cells in children and adults with obesity, highlighting altered cellular metabolism as the causative mechanism. However, there is a paucity of evidence regarding the impact of obesity on the anti-cancer functions of MAIT cells and their behaviour in different adipose tissue depots.

Methods: We sought to evaluate the immuno-metabolic phenotype of MAIT cells in the blood, subcutaneous and omental adipose tissue of patients with obesity undergoing bariatric surgery using flow cytometry, killing assays and single cell metabolic analysis.

Results: We detailed significant alterations in the phenotype, effector function (including the ability to kill cancerous targets) and metabolism of peripheral blood MAIT cells in patients with obesity (mean BMI of 38.73) compared to controls (mean BMI of 25). Additionally, in the patients with obesity there were no differences in MAIT cell frequency, phenotype, cytokine profile or metabolism between omental and subcutaneous adipose tissue highlighting the relevance of subcutaneous adipose tissue as a less invasive site for evaluating immunologic health in obesity.

Conclusion: Our data indicates that MAIT cells are significantly dysregulated in people with obesity, with a loss of protective functions, including the ability to kill cancerous targets. Furthermore, we demonstrate that subcutaneous adipose tissue is quantitatively and qualitatively similar to omental adipose opening up the ability to longitudinally assess adipose tissue MAIT cells in both people with obesity and control groups.