Metabolic control of T cell activation and death in SLE.

Autoimmunity Reviews
David Fernandez, Andras Perl

Abstract

Systemic lupus erythematosus (SLE) is characterized by abnormal T cell activation and death, processes which are crucially dependent on the controlled production of reactive oxygen intermediates (ROI) and of ATP in mitochondria. The mitochondrial transmembrane potential (Deltapsi(m)) has conclusively emerged as a critical checkpoint of ATP synthesis and cell death. Lupus T cells exhibit persistent elevation of Deltapsi(m) or mitochondrial hyperpolarization (MHP) as well as depletion of ATP and glutathione which decrease activation-induced apoptosis and instead predispose T cells for necrosis, thus stimulating inflammation in SLE. NO-induced mitochondrial biogenesis in normal T cells accelerates the rapid phase and reduces the plateau of Ca(2+) influx upon CD3/CD28 co-stimulation, thus mimicking the Ca(2+) signaling profile of lupus T cells. Treatment of SLE patients with rapamycin improves disease activity, normalizes CD3/CD28-induced Ca(2+) fluxing but fails to affect MHP, suggesting that altered Ca(2+) fluxing is downstream or independent of mitochondrial dysfunction. Understanding the molecular basis and consequences of MHP is essential for controlling T cell activation and death signaling in SLE.

References

Nov 20, 1997·The Journal of Clinical Investigation·L GeorgescuM K Crow
Jun 24, 1998·Proceedings of the National Academy of Sciences of the United States of America·E ClementiS Moncada
Jul 1, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·H HentzeA Wendel
Jul 6, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·F PuskasA Perl
Feb 24, 2001·Cellular and Molecular Life Sciences : CMLS·G A Koretzky, N J Boerth
Dec 14, 2001·Proceedings of the National Academy of Sciences of the United States of America·A AlmeidaS Moncada
Jan 31, 2002·Arthritis and Rheumatism·Peter GergelyAndras Perl
Apr 4, 2002·Proceedings of the National Academy of Sciences of the United States of America·Bimal N DesaiStuart L Schreiber
Sep 7, 2002·Antioxidants & Redox Signaling·Andras PerlKatalin Banki
Aug 12, 2005·Current Opinion in Rheumatology·Vasileios C KyttarisGeorge C Tsokos
Oct 26, 2005·Cell Death and Differentiation·M Kundu, C B Thompson
Nov 25, 2005·The New England Journal of Medicine·Maurits DemedtsUNKNOWN IFIGENIA Study Group
Jul 11, 2006·Journal of Cell Science·Enzo Nisoli, Michele O Carruba
Apr 28, 2007·Free Radical Biology & Medicine·Gyorgy NagyAndras Perl

❮ Previous
Next ❯

Citations

Jun 12, 2013·Archivum Immunologiae Et Therapiae Experimentalis·Marcin M KamińskiKarsten Gülow
Oct 22, 2010·Cell Biochemistry and Biophysics·Elena MatteucciOttavio Giampietro
Jun 7, 2011·Arthritis Research & Therapy·Takao Koike
Jun 23, 2012·PloS One·Tianfu WuChandra Mohan
Jan 28, 2014·The Journal of Clinical Investigation·Georgia McDonaldElizabeth C Jury
Jun 25, 2009·Current Opinion in Rheumatology·Andras PerlPaul E Phillips
Jul 30, 2015·Autophagy·Romana T Netea-MaierMihai G Netea
Jul 15, 2015·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Yuxin LiuAndras Perl
Jan 17, 2012·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Andras Perl
Jul 27, 2010·Autoimmunity Reviews·Uriel Katz, Gisele Zandman-Goddard
Jul 20, 2010·Journal of Autoimmunity·Francesca BernuzziGilberto Filaci
Aug 19, 2010·Autoimmunity Reviews·Carlo Selmi
Oct 27, 2009·Autoimmunity Reviews·Patrick S C LeungMi-Hua Tao
Oct 2, 2009·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Emily WaltersBruce F Kimler
Mar 24, 2009·Trends in Molecular Medicine·Bernhard KadenbachSebastian Vogt
Apr 28, 2009·Autoimmunity Reviews·Carlo PerriconeRoberto Perricone
Dec 8, 2009·Autoimmunity·Gabriela Gorelik, Bruce Richardson
Apr 12, 2015·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Zhi-wei LaiAndras Perl
Oct 7, 2016·Current Rheumatology Reports·Seung-Chul ChoiLaurence Morel
Apr 1, 2017·Nature Reviews. Rheumatology·Laurence Morel
Jun 10, 2009·Expert Opinion on Pharmacotherapy·Lisa Francis, Andras Perl
Feb 4, 2019·Annals of the Rheumatic Diseases·Kevin L WinthropDaniel E Furst
Jan 17, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Marina PierdominiciElena Ortona
Mar 26, 2010·Expert Opinion on Therapeutic Targets·Daoxin MaMing Hou
Aug 6, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhi-Wei LaiAndras Perl
Jun 20, 2018·Frontiers in Immunology·Francesco UrsiniRoberto De Giorgio
Apr 25, 2019·BioMed Research International·Wei LiuSheng-Guang Li
Feb 19, 2020·Current Rheumatology Reports·Kiley BaxJulian L Ambrus
Mar 14, 2019·Frontiers in Immunology·Manuel Martínez-Bueno, Marta E Alarcón-Riquelme
Jul 28, 2018·Frontiers in Immunology·Anusha AngajalaMing Tan

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Caspases in Metabolic Diseases

Caspases, the family of cysteine proteases are involved in programmed cell death, but their role in metabolic diseases, inflammation and immunity has been of interested. Discover the latest research on caspases in metabolic diseases here.

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis