This article is a commentary on:
T Cell Metabolism: A New Perspective on Th17/Treg Cell Imbalance in Systemic Lupus Erythematosus
Jiamei Jin
Xiaogu Liu*A commentary on
T cell metabolism: a new perspective on Th17/Treg cell imbalance in systemic lupus erythematosus
by Shan J, Jin H and Xu Y (2020) Front. Immunol. 11:1027. doi: 10.3389/fimmu.2020.01027
1 Introduction
A study entitled “T cell metabolism: A new perspective on Th17/Treg cell imbalance in systemic lupus erythematosus” was published in Frontiers in Immunology by Shan J and his colleagues (1). The article’s summary claims that Th17/regulatory T cells (Treg) play a role in the initiation and progression of systemic lupus erythematosus (SLE). Mounting evidence suggests that metabolic pathways participate in inflammatory responses in SLE by regulating T-cell differentiation and function. A novel SLE treatment reverses the Th17/Treg imbalance by targeting metabolic pathways. SLE patients have distinct T-cell metabolic patterns, such as glycolysis, lipid synthesis, and glutaminolysis, all of which are conducive to Th17 cell differentiation and function. Conversely, Tregs rely more on energy from oxidative metabolism and fatty acid oxidation.
Under the subheading of Metabolic control of Th17/Treg balance, this article first described “Tregs, on the other hand, were found to rely more on fatty acid oxidation and oxidative phosphorylation to supply energy” and then described “Conversely, inhibition of fatty acid oxidation results in diminished differentiation of Th17 cells but increased development of Tregs.” There is an apparent inconsistency between the two accounts.
Two references cited here show that Tregs not only oxidize lipids at a high rate, but also oxidize pyruvate derived from glycolysis. Specifically, Teffs (Th1 and Th17) depend on glycolysis, whereas Tregs have higher flexibility in fuel choice and can oxidize glucose in addition to fats (2). Moreover, Tregs and memory CD8+ cells preferably rely on mitochondrial fatty acid oxidation to meet cell energy requirements; their energy production pathways are binary: oxidative fatty acid uptake and glycolysis/glutamine decomposition, respectively (3). Numerous studies have shown that Tregs depend on fatty acid oxidation for energy supply, and inhibition of fatty acid oxidation can hinder Treg development (4–8). Hence, the words “diminished” and “increased” should switch places in the description above.
Further studies are needed to investigate T cells’ metabolic abnormalities in SLE patients, their role in disease progression, and their response to therapy, especially activities interfering with the Th17/Treg cell imbalance. We believe that the summary by Shan J and his colleagues will help us better understand the relationship between metabolic abnormalities in T cells and the Th17/Treg balance. However, this review needs to be written more rigorously to demonstrate that the metabolic profile of T cells underlies the Th17/Treg cell imbalance in SLE patients.
Author contributions
JJ conceived the original idea and wrote the manuscript with support from XL. All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.
Funding
This work was funded by the 2021 Zhejiang Provincial Basic Public Welfare Research Program (Y19H270039) and the 2023 Zhejiang Provincial Natural Science Foundation (LQ23H270007), Zhejiang Provincial Natural Science Foundation Committee Office.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1. Shan J, Jin H, Xu Y. T Cell metabolism: a new perspective on Th17/Treg cell imbalance in systemic lupus erythematosus. Front Immunol (2020) 11:1027. doi: 10.3389/fimmu.2020.01027
2. Gerriets VA, Kishton RJ, Nichols AG, Macintyre AN, Inoue M, Ilkayeva O, et al. Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation. J Clin Invest (2015) 125:194–207. doi: 10.1172/JCI76012
3. Gualdoni GA, KA M, Göschl L, Boucheron N, Ellmeier W, Zlabinger GJ. The AMP analog AICAR modulates the Treg/Th17 axis through enhancement of fatty acid oxidation. FASEB J (2016) 30:3800–9. doi: 10.1096/fj.201600522R
4. Zhang S, Gang X, Yang S, Cui M, Sun L, Li Z, et al. The alterations in and the role of the Th17/Treg balance in metabolic diseases. Front Immunol (2021) 12:678355. doi: 10.3389/fimmu.2021.678355
5. Cluxton D, Petrasca A, Moran B, Fletcher JM. Differential regulation of human treg and Th17 cells by fatty acid synthesis and glycolysis. Front Immunol (2019) 10:115. doi: 10.3389/fimmu.2019.00115
6. Shi H, Chi H. Metabolic control of treg cell stability, plasticity, and tissue-specific heterogeneity. Front Immunol (2019) 10:2716. doi: 10.3389/fimmu.2019.02716
7. Yan Y, Huang L, Liu Y, Yi M, Chu Q, Jiao D, et al. Metabolic profiles of regulatory T cells and their adaptations to the tumor microenvironment: implications for antitumor immunity. J Hematol Oncol (2022) 15(1):104. doi: 10.1186/s13045-022-01322-3
Keywords: cell metabolism, T helper 17 cells, regulatory T cells, systemic lupus erythematosus, fatty acid oxidation
Citation: Jin J and Liu X (2023) Commentary: T cell metabolism: a new perspective on Th17/Treg cell imbalance in systemic lupus erythematosus. Front. Immunol. 14:1164761. doi: 10.3389/fimmu.2023.1164761
Received: 13 February 2023; Accepted: 12 April 2023;
Published: 25 April 2023.
Edited by:
Coziana Ciurtin, University College London, United KingdomReviewed by:
Maria N. Navarro, Spanish National Research Council (CSIC), SpainCopyright © 2023 Jin and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Xiaogu Liu, bGl1eGlhb2d1QDEyNi5jb20=