Transcriptional factor ICER promotes glutaminolysis and the generation of Th17 cells

Proceedings of the National Academy of Sciences of the United States of America
Michihito KonoGeorge C Tsokos

Abstract

Glutaminolysis is a well-known source of energy for effector T cells but its contribution to each T cell subset and the mechanisms which are responsible for the control of involved metabolic enzymes are not fully understood. We report that Th17 but not Th1, Th2, or Treg cell induction in vitro depends on glutaminolysis and the up-regulation of glutaminase 1 (Gls1), the first enzyme in the glutaminolysis pathway. Both pharmacological and siRNA-based selective inhibition of Gls1 reduced in vitro Th17 differentiation and reduced the CD3/TCR-mediated increase of the mammalian target of rapamycin complex 1 activity. Treatment of mice with a Gls1 inhibitor ameliorated experimental autoimmune encephalomyelitis. Furthermore, RAG1-deficient mice that received Gls1-shRNA-transfected 2D2 T cells had reduced experimental autoimmune encephalomyelitis scores compared with those that received control-shRNA-treated cells. Next we found that T cells deficient in inducible cAMP early repressor (ICER), a transcriptional factor known to promote Th17 differentiation, display reduced activity of oxidative phosphorylation rates in the presence of glutamine and reduced Gls1 expression, both of which could be restored by ICER overexpression. Finally, w...Continue Reading

References

Feb 7, 1992·Cell·N S Foulkes, P Sassone-Corsi
Mar 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Xinmin ZhangMarc Montminy
Jan 10, 2009·Annual Review of Immunology·Thomas KornVijay K Kuchroo
Mar 27, 2009·The Journal of Investigative Dermatology·Antonella Di CesareFrank O Nestle
Mar 3, 2010·Annual Review of Immunology·Jinfang ZhuWilliam E Paul
Jul 24, 2010·Nephrology·Joshua D OoiStephen R Holdsworth
Jul 12, 2012·Nature Biotechnology·Heesun CheongCraig B Thompson
Jan 10, 2013·Annual Review of Immunology·Nancie J MacIverJeffrey C Rathmell
Mar 29, 2014·The Journal of Clinical Investigation·Tomohiro KogaGeorge C Tsokos
Jun 26, 2014·Nature Reviews. Immunology·Kristen N Pollizzi, Jonathan D Powell
Aug 29, 2014·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Dennis BotmanCornelis J F Van Noorden
Dec 2, 2014·The Journal of Clinical Investigation·Valerie A GerrietsJeffrey C Rathmell
Feb 13, 2015·Science Translational Medicine·Yiming YinLaurence Morel
Feb 15, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ulf H BeierWayne W Hancock
Aug 12, 2015·The Journal of Experimental Medicine·Michael D BuckErika L Pearce
Nov 26, 2015·Oncogene·L JinS Kang
Apr 10, 2016·European Journal of Immunology·Noé Rodríguez-RodríguezJosé C Crispín
May 20, 2016·Nature Immunology·Ryan NewtonLaurence A Turka
Aug 26, 2016·Proceedings of the National Academy of Sciences of the United States of America·Amira ElgogaryAnne Le
Sep 30, 2016·Nature Communications·Nobuya YoshidaGeorge C Tsokos
Mar 17, 2017·Annual Review of Biomedical Engineering·Lifeng YangDeepak Nagrath
Mar 28, 2017·The Journal of Clinical Investigation·Arimichi OkazakiOthon Iliopoulos
Apr 1, 2017·Nature Reviews. Rheumatology·Laurence Morel
Apr 13, 2017·Arthritis Research & Therapy·Soshi TakahashiAkio Morinobu

❮ Previous
Next ❯

Citations

Feb 17, 2019·Clinical and Experimental Immunology·X TengL Morel
Jun 19, 2019·Journal of Cellular and Molecular Medicine·Jing LiJianguo Hu
Dec 17, 2019·Current Opinion in Rheumatology·Michihito KonoGeorge C Tsokos
Mar 13, 2020·Immunological Reviews·Xiangyu TengLaurence Morel
Aug 29, 2018·Proceedings of the National Academy of Sciences of the United States of America·Michihito KonoGeorge C Tsokos
Apr 8, 2020·Immunometabolism·Milena VukelicGeorge C Tsokos
Aug 25, 2020·The Journal of Clinical Investigation·Xichun XiaYunfei Gao
Jun 21, 2019·JCI Insight·Michihito KonoGeorge C Tsokos
Jan 18, 2020·Nature Reviews. Rheumatology·Amir Sharabi, George C Tsokos
Jul 17, 2020·Science China. Life Sciences·Guan YangWenkai Ren
Oct 9, 2018·Immunological Reviews·Ann M JosephGregory F Sonnenberg
Nov 1, 2020·International Journal of Molecular Sciences·Xiaoliang Zhu, Jinfang Zhu
Nov 13, 2020·Clinical Reviews in Allergy & Immunology·Tingting WangXuan Zhang
Feb 10, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Diana C Contreras HealeyJeffrey C Rathmell
Mar 12, 2021·Frontiers in Immunology·Michihito KonoGeorge C Tsokos
Jul 11, 2020·Cell Metabolism·Beth Kelly, Erika L Pearce
Apr 4, 2021·Nutrients·Jian TanLaurence Macia
Mar 26, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wenliang PanGeorge C Tsokos
Apr 2, 2021·The FEBS Journal·Gina Papadopoulou, Georgina Xanthou
Apr 11, 2021·Journal of the Formosan Medical Association = Taiwan Yi Zhi·Hong-Tai Tzeng, I-Tsu Chyuan
May 18, 2021·Frontiers in Immunology·Sally A ClaytonAndrew R Clark
Jun 13, 2021·Autoimmunity Reviews·Marc Scherlinger, George C Tsokos
Jul 30, 2021·Frontiers in Immunology·Siwen ZhangGuixia Wang
Aug 28, 2021·Biological Chemistry·Sudheendra Hebbar Subramanyam, Klaus Tenbrock

❮ Previous
Next ❯

Related Concepts

Related Feeds

Related Papers

Endocrine, Metabolic & Immune Disorders Drug Targets
Myung-Ja KwonZuoming Sun
The Journal of Immunology : Official Journal of the American Association of Immunologists
Violeta RusHorea G Rus
Nature Communications
Nobuya YoshidaGeorge C Tsokos
Nihon Rinshō Men'eki Gakkai kaishi = Japanese journal of clinical immunology
Christian KlemannTakashi Yamamura
© 2022 Meta ULC. All rights reserved