PP2A dephosphorylates Elf-1 and determines the expression of CD3zeta and FcRgamma in human systemic lupus erythematosus T cells.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Yuang-Taung JuangGeorge C Tsokos

Abstract

T cells from patients with systemic lupus erythematosus are characterized by decreased expression of CD3zeta-chain and increased expression of FcRgamma-chain, which becomes part of the CD3 complex and contributes to aberrant signaling. Elf-1 enhances the expression of CD3zeta, whereas it suppresses the expression of FcRgamma gene and lupus T cells have decreased amounts of DNA-binding 98 kDa form of Elf-1. We show that the aberrantly increased PP2A in lupus T cells dephosphorylates Elf-1 at Thr-231. Dephosphorylation results in limited expression and binding of the 98 kDa Elf-1 form to the CD3zeta and FcRgamma promoters. Suppression of the expression of the PP2A leads to increased expression of CD3zeta and decreased expression of FcRgamma genes and correction of the early signaling response. Therefore, PP2A serves as a central determinant of abnormal T cell function in human lupus and may represent an appropriate treatment target.

References

Aug 1, 1991·Clinical Immunology and Immunopathology·Y TadaY Niho
Nov 1, 1982·Arthritis and Rheumatism·E M TanR J Winchester
Sep 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·M TakahashiY Ono
Mar 9, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yuang-Taung JuangGeorge C Tsokos
Apr 24, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chiharu NishiyamaChisei Ra
Nov 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yuang-Taung JuangG C Tsokos
May 6, 2003·Biochimica Et Biophysica Acta·Christine Van Hoof, Jozef Goris
May 10, 2003·Trends in Immunology·George C TsokosYuang-Taung Juang
Nov 26, 2003·Blood Cells, Molecules & Diseases·H Daniel Lacorazza, Stephen D Nimer
Jun 10, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sandeep KrishnanGeorge C Tsokos
Aug 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Vasileios C KyttarisGeorge C Tsokos
Aug 17, 2005·Current Drug Targets. Inflammation and Allergy·Tsutomu TakeuchiKouichi Amano
Aug 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sandeep KrishnanGeorge C Tsokos
Oct 15, 2005·The Journal of Clinical Investigation·Christina G KatsiariGeorge C Tsokos
May 23, 2006·Seminars in Immunology·Sandeep KrishnanGeorge C Tsokos
Oct 20, 2006·The Journal of Biological Chemistry·Simon R Tew, Timothy E Hardingham
Nov 23, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bhabadeb ChowdhuryGeorge C Tsokos
Jan 12, 2007·Endocrine, Metabolic & Immune Disorders Drug Targets·David FernandezAndras Perl
Sep 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yuang-Taung JuangGeorge C Tsokos

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Citations

Apr 19, 2012·The Journal of Biological Chemistry·Jeoung-Eun ParkLinda K Myers
Jun 5, 2013·Nature Reviews. Rheumatology·José C CrispínGeorge C Tsokos
Sep 29, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Motofumi KumazoeHirofumi Tachibana
Jun 6, 2018·Frontiers in Immunology·Takayuki KatsuyamaVaishali R Moulton
May 30, 2019·International Journal of Molecular Sciences·Eun-Ju LeeYong-Gil Kim
Mar 13, 2020·JCI Insight·Esra MeidanGeorge C Tsokos
Sep 10, 2013·PloS One·Alexandros P GrammatikosGeorge C Tsokos
Oct 9, 2013·Nature Reviews. Rheumatology·Andras Perl
Mar 16, 2019·Expert Review of Clinical Immunology·Tomohiro KogaGeorge C Tsokos
May 16, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ying DingThomas R Malek
Feb 25, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Katsue SunahoriGeorge C Tsokos
Jul 13, 2011·Proceedings of the National Academy of Sciences of the United States of America·José C CrispínGeorge C Tsokos
Apr 3, 2014·The Journal of Biological Chemistry·Kamalpreet NagpalGeorge C Tsokos
Jun 25, 2009·Current Opinion in Rheumatology·Andras PerlPaul E Phillips
Mar 14, 2017·Nature Reviews. Nephrology·Abel Suárez-FueyoGeorge C Tsokos
May 28, 2014·Journal of Immunology Research·Anselm Mak, Nien Yee Kow
Jan 18, 2020·Nature Reviews. Rheumatology·Amir Sharabi, George C Tsokos

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