Glutamine Metabolism in Th17/Treg Cell Fate: Applications in Th17 Cell-associated Diseases

Overview

Journal Sci China Life Sci

Specialties Biology
Science

Date 2020 Jul 17

PMID 32671630

Citations 17

Authors

Guan Yang

Yaoyao Xia

Wenkai Ren

Affiliations

Soon will be listed here.

Abstract

Alteration in the Th17/Treg cell balance is implicated in various autoimmune diseases and these disease-associated pathologies. Increasing investigations have shown that glutamine metabolism regulates the differentiation of Th17 and Treg cells. Here we summarize the mechanisms by which glutamine metabolism regulates Th17/Treg cell fate. Some examples of a glutamine metabolism-dependent modulation of the development and progression of several Th17 Treg cell-associated diseases are provided afterward. This review will provide a comprehensive understanding of the importance of glutamine metabolism in the fate of Th17 Treg cell differentiation.

Citing Articles

Regulatory T Cell Metabolism: A Promising Therapeutic Target for Cancer Treatment?.

Kim J, Li J, Wei J, Lim S Immune Netw. 2025; 25(1):e13.

PMID: 40078783 PMC: 11896657. DOI: 10.4110/in.2025.25.e13.

Influence of Foliar Application of Nanoparticles on Low Temperature Resistance of Rice Seedlings.

Ullah S, Ikram M, Xiao J, Khan A, Din I, Huang J Plants (Basel). 2024; 13(21).

PMID: 39519868 PMC: 11548232. DOI: 10.3390/plants13212949.

The role of Th/Treg immune cells in osteoarthritis.

Wen Z, Qiu L, Ye Z, Tan X, Xu X, Lu M Front Immunol. 2024; 15:1393418.

PMID: 39364408 PMC: 11446774. DOI: 10.3389/fimmu.2024.1393418.

Metabolism at the crossroads of inflammation and fibrosis in chronic kidney disease.

Miguel V, Shaw I, Kramann R Nat Rev Nephrol. 2024; 21(1):39-56.

PMID: 39289568 DOI: 10.1038/s41581-024-00889-z.

The immune landscape of the inflamed joint defined by spectral flow cytometry.

Attrill M, Shinko D, Alexiou V, Kartawinata M, Wedderburn L, Pesenacker A Clin Exp Immunol. 2024; 218(3):221-241.

PMID: 39101538 PMC: 11557149. DOI: 10.1093/cei/uxae071.

References

Alberghina L, Gaglio D . Redox control of glutamine utilization in cancer. Cell Death Dis. 2014; 5:e1561. PMC: 4454159. DOI: 10.1038/cddis.2014.513. View

Almeida L, Lochner M, Berod L, Sparwasser T . Metabolic pathways in T cell activation and lineage differentiation. Semin Immunol. 2016; 28(5):514-524. DOI: 10.1016/j.smim.2016.10.009. View

Altman B, Stine Z, Dang C . From Krebs to clinic: glutamine metabolism to cancer therapy. Nat Rev Cancer. 2017; 16(11):749. DOI: 10.1038/nrc.2016.114. View

Angelin A, Gil-de-Gomez L, Dahiya S, Jiao J, Guo L, Levine M . Foxp3 Reprograms T Cell Metabolism to Function in Low-Glucose, High-Lactate Environments. Cell Metab. 2017; 25(6):1282-1293.e7. PMC: 5462872. DOI: 10.1016/j.cmet.2016.12.018. View

Araujo L, Khim P, Mkhikian H, Mortales C, Demetriou M . Glycolysis and glutaminolysis cooperatively control T cell function by limiting metabolite supply to N-glycosylation. Elife. 2017; 6. PMC: 5257256. DOI: 10.7554/eLife.21330. View

Arellano B, Graber D, Sentman C . Regulatory T cell-based therapies for autoimmunity. Discov Med. 2016; 22(119):73-80. PMC: 5573148. View

Ben-Sahra I, Howell J, Asara J, Manning B . Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1. Science. 2013; 339(6125):1323-8. PMC: 3753690. DOI: 10.1126/science.1228792. View

Beringer A, Noack M, Miossec P . IL-17 in Chronic Inflammation: From Discovery to Targeting. Trends Mol Med. 2016; 22(3):230-241. DOI: 10.1016/j.molmed.2016.01.001. View

Berod L, Friedrich C, Nandan A, Freitag J, Hagemann S, Harmrolfs K . De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells. Nat Med. 2014; 20(11):1327-33. DOI: 10.1038/nm.3704. View

10.

Bhutia Y, Babu E, Ramachandran S, Ganapathy V . Amino Acid transporters in cancer and their relevance to "glutamine addiction": novel targets for the design of a new class of anticancer drugs. Cancer Res. 2015; 75(9):1782-8. DOI: 10.1158/0008-5472.CAN-14-3745. View

11.

Birsoy K, Wang T, Chen W, Freinkman E, Abu-Remaileh M, Sabatini D . An Essential Role of the Mitochondrial Electron Transport Chain in Cell Proliferation Is to Enable Aspartate Synthesis. Cell. 2015; 162(3):540-51. PMC: 4522279. DOI: 10.1016/j.cell.2015.07.016. View

12.

Broer A, Rahimi F, Broer S . Deletion of Amino Acid Transporter ASCT2 (SLC1A5) Reveals an Essential Role for Transporters SNAT1 (SLC38A1) and SNAT2 (SLC38A2) to Sustain Glutaminolysis in Cancer Cells. J Biol Chem. 2016; 291(25):13194-205. PMC: 4933233. DOI: 10.1074/jbc.M115.700534. View

13.

Bunse L, Pusch S, Bunse T, Sahm F, Sanghvi K, Friedrich M . Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate. Nat Med. 2018; 24(8):1192-1203. DOI: 10.1038/s41591-018-0095-6. View

14.

Carr E, Kelman A, Wu G, Gopaul R, Senkevitch E, Aghvanyan A . Glutamine uptake and metabolism are coordinately regulated by ERK/MAPK during T lymphocyte activation. J Immunol. 2010; 185(2):1037-44. PMC: 2897897. DOI: 10.4049/jimmunol.0903586. View

15.

Chantranupong L, Scaria S, Saxton R, Gygi M, Shen K, Wyant G . The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway. Cell. 2016; 165(1):153-164. PMC: 4808398. DOI: 10.1016/j.cell.2016.02.035. View

16.

Chen W, Jin W, Hardegen N, Lei K, Li L, Marinos N . Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med. 2003; 198(12):1875-86. PMC: 2194145. DOI: 10.1084/jem.20030152. View

17.

Cheong H, Lindsten T, Wu J, Lu C, Thompson C . Ammonia-induced autophagy is independent of ULK1/ULK2 kinases. Proc Natl Acad Sci U S A. 2011; 108(27):11121-6. PMC: 3131371. DOI: 10.1073/pnas.1107969108. View

18.

Cooper A, Kuhara T . α-Ketoglutaramate: an overlooked metabolite of glutamine and a biomarker for hepatic encephalopathy and inborn errors of the urea cycle. Metab Brain Dis. 2013; 29(4):991-1006. PMC: 4020999. DOI: 10.1007/s11011-013-9444-9. View

19.

Dang L, Su S . Isocitrate Dehydrogenase Mutation and (R)-2-Hydroxyglutarate: From Basic Discovery to Therapeutics Development. Annu Rev Biochem. 2017; 86:305-331. DOI: 10.1146/annurev-biochem-061516-044732. View

20.

DeBerardinis R, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S . Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci U S A. 2007; 104(49):19345-50. PMC: 2148292. DOI: 10.1073/pnas.0709747104. View