Pharma Focus Asia

High Glucose Promotes Regulatory T Cell Differentiation

Elise Pitmon, Eileen Victoria Meehan, Elham Ahmadi, Adam J. Adler, Kepeng Wang

Abstract


The consumption of processed foods and sugary sodas in Western diets correlates with an increased incidence of obesity, metabolic syndromes such as type 2 diabetes, cardiovascular diseases, and autoimmune diseases including inflammatory bowel disease and rheumatoid arthritis. All these diseases have an inflammatory component, of which T lymphocytes can play a critical role in driving.

Introduction


The consumption of sugar has been rising in Western countries. In parallel, the incidences of obesity, metabolic syndrome, and cardiovascular diseases have also increased, as has the prevalence of autoimmune diseases such as inflammatory bowel disease (IBD), multiple sclerosis (MS), and rheumatoid arthritis (RA). Indeed, the trend towards increasing autoimmune disease incidence can be seen in countries with a high pace of socio-economic improvement and westernization.

Methods

Mice
C57BL/6 mice were obtained from the Jackson Laboratory and housed in a specific pathogen-free environment. Both male and female mice were used in experiments, all of which were reviewed and approved by the UConn Health IACUC.

T cell culture


Naïve CD4+ T cells were isolated and purified from the spleens of C57BL/6 mice using a naïve CD4+ T cell isolation kit (Stemcell Technologies, Cat # 19765), and then cultured in 96-well round bottom plates with 0.5 μg/mL plate-bound anti-CD3 (Biolegend, Cat # 100340).


Discussion:


Naïve and activated T cells have different metabolic substrate preferences [11, 19]. In particular, T cells switch from oxidative phosphorylation to aerobic glycolysis upon activation. Aerobic glycolysis is required for T cell effector function [19]. Uptake of glucose by Glut1 is followed by glycolytic breakdown to pyruvate with the net production of two ATP molecules. In non-proliferating and terminally differentiated T cells, pyruvate is further processed through the tricarboxylic acid (TCA) cycle to generate NADH and FADH2, which are in turn oxidized to produce 36 molecules of ATP per glucose molecule. In activated effector T cells, however, glucose-generated pyruvate is converted into lactate, even though sufficient oxygen is available for oxidative phosphorylation.

Acknowledgments:


We thank Dr. Evan Jellison and Ms. Li Zhu at the UConn Health Flow Cytometry Core Facility for technical assistance. We also thank Dr. Anthony Vella, Dr. Robert Clark, and Dr. Ju Chen at UConn Health for advice and technical assistance, and Drs. Christopher Bonin and Geneva Hargis for scientific editing.

Citation: Pitmon E, Meehan EV, Ahmadi E, Adler AJ, Wang K (2023) High glucose promotes regulatory T cell differentiation. PLoS ONE 18(2): e0280916. https://doi.org/10.1371/journal.pone.0280916

Editor: Pierre Bobé, Universite Paris-Saclay, FRANCE

Received: April 12, 2022; Accepted: January 12, 2023; Published: February 2, 2023.

Copyright: © 2023 Pitmon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper.

Funding: This work was supported by a T90 training grant to E.P. and National Institute of Health/National Cancer Institute (NIH/NCI R01CA262430) to K.W. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Competing interests: The authors declare no conflict of interest.

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