Immunometabolism regulates TCR recycling and iNKT cell functions

Science Signaling
Sicheng FuLi Bai

Abstract

Invariant natural killer T (iNKT) cells are innate-like T lymphocytes that express an invariant T cell receptor (TCR), which recognizes glycolipid antigens presented on CD1d molecules. These cells are phenotypically and functionally distinct from conventional T cells. When we characterized the metabolic activity of iNKT cells, consistent with their activated phenotype, we found that they had much less mitochondrial respiratory capacity but increased glycolytic activity in comparison to naïve conventional CD4+ T cells. After TCR engagement, iNKT cells further increased aerobic glycolysis, which was important for the expression of interferon-γ (IFN-γ). Glycolytic metabolism promoted the translocation of hexokinase-II to mitochondria and the activation of mammalian target of rapamycin complex 2 (mTORC2). Inhibiting glycolysis reduced the activity of Akt and PKCθ, which inhibited TCR recycling and accumulation within the immune synapse. Diminished TCR accumulation in the immune synapse reduced the activation of proximal and distal TCR signaling pathways and IFN-γ production in activated iNKT cells. Our studies demonstrate that glycolytic metabolism augments TCR signaling duration and IFN-γ production in iNKT cells by increasing TCR...Continue Reading

References

Mar 15, 1996·The Journal of Clinical Investigation·K Panneerselvam, H H Freeze
Sep 21, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·S M TahirM A Exley
Dec 26, 2001·The Journal of Biological Chemistry·John G PastorinoJan B Hoek
Mar 6, 2002·The Journal of Experimental Medicine·Gloria Gonzalez-AseguinolazaMoriya Tsuji
Jul 18, 2002·Immunity·Kenneth A FrauwirthCraig B Thompson
Jan 25, 2003·Annual Review of Immunology·Masaru TaniguchiHiroshi Wakao
Oct 22, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Aleksandar K StanicSebastian Joyce
Dec 4, 2003·Nature Reviews. Immunology·Johannes B Huppa, Mark M Davis
Mar 25, 2004·Nature Reviews. Immunology·Dale I GodfreyLuc Van Kaer
Oct 21, 2004·Journal of the American Chemical Society·Randal D GoffPaul B Savage
Dec 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rodney MorganBaiyong Li
Feb 19, 2005·Science·D D SarbassovDavid M Sabatini
Feb 22, 2005·Proceedings of the National Academy of Sciences of the United States of America·Karl O A YuSteven A Porcelli
Mar 10, 2005·International Journal of Cancer. Journal International Du Cancer·Johan W MollingAlfons J M van den Eertwegh
Mar 18, 2005·Annual Review of Immunology·Mitchell Kronenberg
Apr 1, 2005·PLoS Biology·Frederic GeissmannDan R Littman
Oct 22, 2005·Nature Reviews. Immunology·Casey J FoxCraig B Thompson
May 20, 2006·Blood·Markus MunderAnthony D Ho
Jun 6, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marina von EssenCarsten Geisler
Jul 11, 2006·Nature Reviews. Molecular Cell Biology·Bruce T SeetTony Pawson
Dec 8, 2006·Annual Review of Immunology·Albert BendelacLuc Teyton
Jun 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·Ya-Jen ChangAlice L Yu
Aug 29, 2007·Immunity·Russell G Jones, Craig B Thompson
May 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hans J J van der VlietMark A Exley
Jan 28, 2009·The Journal of Experimental Medicine·Jürgen KuballPhilip D Greenberg
Jul 23, 2009·The International Journal of Biochemistry & Cell Biology·Katarzyna KoziełMariusz R Wieckowski
Aug 22, 2009·Nature Reviews. Molecular Cell Biology·Barth D Grant, Julie G Donaldson
May 26, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Juan-Carlos Rodríguez-PradosLisardo Boscá
Nov 3, 2010·Annual Review of Pathology·Justin I Odegaard, Ajay Chawla
Jan 19, 2011·The Journal of Experimental Medicine·Amparo WolfAbhijit Guha
Jan 27, 2011·Nature Reviews. Immunology·Stuart P BerzinsAlan G Baxter
Feb 15, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ryan D MichalekJeffrey C Rathmell
Feb 18, 2011·Proceedings of the National Academy of Sciences of the United States of America·Qian SunHongbing Zhang

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Citations

Jun 12, 2020·Cellular & Molecular Immunology·Huimin Zhang, Li Bai
Aug 9, 2020·Molecular Cancer·Song-Yang WuZhi-Ming Shao
Dec 8, 2020·Frontiers in Cardiovascular Medicine·Ibrahim AlZaimAhmed F El-Yazbi
Mar 24, 2021·Proceedings of the National Academy of Sciences of the United States of America·Xiufang WengChyung-Ru Wang
Apr 21, 2021·Current Opinion in Pharmacology·Gustavo Gastão DavanzoPedro Manoel M Moraes-Vieira
Oct 5, 2021·Frontiers in Cellular and Infection Microbiology·Andrew J JezewskiAudrey R Odom John
Nov 14, 2021·Proceedings of the National Academy of Sciences of the United States of America·Huimin ZhangLi Bai

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