Literature DB >> 20339032

Protein kinase C-theta mediates negative feedback on regulatory T cell function.

Alexandra Zanin-Zhorov1, Yi Ding, Sudha Kumari, Mukundan Attur, Keli L Hippen, Maryanne Brown, Bruce R Blazar, Steven B Abramson, Juan J Lafaille, Michael L Dustin.   

Abstract

T cell receptor (TCR)-dependent regulatory T cell (Treg) activity controls effector T cell (Teff) function and is inhibited by the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). Protein kinase C-theta (PKC-theta) recruitment to the immunological synapse is required for full Teff activation. In contrast, PKC-theta was sequestered away from the Treg immunological synapse. Furthermore, PKC-theta blockade enhanced Treg function, demonstrating PKC-theta inhibits Treg-mediated suppression. Inhibition of PKC-theta protected Treg from inactivation by TNF-alpha, restored activity of defective Treg from rheumatoid arthritis patients, and enhanced protection of mice from inflammatory colitis. Treg freed of PKC-theta-mediated inhibition can function in the presence of inflammatory cytokines and thus have therapeutic potential in control of inflammatory diseases.

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Year:  2010        PMID： 20339032      PMCID： PMC2905626          DOI： 10.1126/science.1186068

Source DB:  PubMed          Journal:  Science        ISSN： 0036-8075            Impact factor:   47.728


  30 in total

1.  The immunological synapse: a molecular machine controlling T cell activation.

Authors:  A Grakoui; S K Bromley; C Sumen; M M Davis; A S Shaw; P M Allen; M L Dustin
Journal:  Science       Date:  1999-07-09       Impact factor: 47.728

Review 2.  The lifestyle of naturally occurring CD4+ CD25+ Foxp3+ regulatory T cells.

Authors:  Ethan M Shevach; Richard A DiPaolo; John Andersson; Dong-Mei Zhao; Geoffrey L Stephens; Angela M Thornton
Journal:  Immunol Rev       Date:  2006-08       Impact factor: 12.988

Review 3.  Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases.

Authors:  P J Barnes; M Karin
Journal:  N Engl J Med       Date:  1997-04-10       Impact factor: 91.245

4.  Three-dimensional segregation of supramolecular activation clusters in T cells.

Authors:  C R Monks; B A Freiberg; H Kupfer; N Sciaky; A Kupfer
Journal:  Nature       Date:  1998-09-03       Impact factor: 49.962

5.  PKC-theta is required for TCR-induced NF-kappaB activation in mature but not immature T lymphocytes.

Authors:  Z Sun; C W Arendt; W Ellmeier; E M Schaeffer; M J Sunshine; L Gandhi; J Annes; D Petrzilka; A Kupfer; P L Schwartzberg; D R Littman
Journal:  Nature       Date:  2000-03-23       Impact factor: 49.962

6.  Selective modulation of protein kinase C-theta during T-cell activation.

Authors:  C R Monks; H Kupfer; I Tamir; A Barlow; A Kupfer
Journal:  Nature       Date:  1997-01-02       Impact factor: 49.962

7.  Cord blood CD4(+)CD25(+)-derived T regulatory cell lines express FoxP3 protein and manifest potent suppressor function.

Authors:  Wayne R Godfrey; Darrin J Spoden; Ying G Ge; Seth R Baker; Baoling Liu; Bruce L Levine; Carl H June; Bruce R Blazar; Stephen B Porter
Journal:  Blood       Date:  2004-09-16       Impact factor: 22.113

8.  Engagement of protein kinase C-theta in interferon signaling in T-cells.

Authors:  Kishore K Srivastava; Sandeep Batra; Antonella Sassano; Yongzhong Li; Beata Majchrzak; Hiroaki Kiyokawa; Amnon Altman; Eleanor N Fish; Leonidas C Platanias
Journal:  J Biol Chem       Date:  2004-05-18       Impact factor: 5.157

9.  A critical role for transforming growth factor-beta but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RB(low) CD4+ T cells.

Authors:  F Powrie; J Carlino; M W Leach; S Mauze; R L Coffman
Journal:  J Exp Med       Date:  1996-06-01       Impact factor: 14.307

10.  Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy.

Authors:  Michael R Ehrenstein; Jamie G Evans; Animesh Singh; Samantha Moore; Gary Warnes; David A Isenberg; Claudia Mauri
Journal:  J Exp Med       Date:  2004-07-26       Impact factor: 14.307
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  153 in total

Review 1.  The immunological synapse.

Authors:  Michael L Dustin
Journal:  Cancer Immunol Res       Date:  2014-11       Impact factor: 11.151

2.  Blocking IL-21 signaling ameliorates xenogeneic GVHD induced by human lymphocytes.

Authors:  Keli L Hippen; Christoph Bucher; Dawn K Schirm; Amanda M Bearl; Ty Brender; Kathy A Mink; Kimberly S Waggie; Regis Peffault de Latour; Anne Janin; Julie M Curtsinger; Stacey R Dillon; Jeffrey S Miller; Gerard Socie; Bruce R Blazar
Journal:  Blood       Date:  2011-11-10       Impact factor: 22.113

Review 3.  Role of T cell-nuclear factor κB in transplantation.

Authors:  Luciana L Molinero; Maria-Luisa Alegre
Journal:  Transplant Rev (Orlando)       Date:  2011-11-08       Impact factor: 3.943

Review 4.  Integrin signalling and function in immune cells.

Authors:  Yanbo Zhang; Hongyan Wang
Journal:  Immunology       Date:  2012-04       Impact factor: 7.397

5.  PKC-θ: hitting the bull's eye.

Authors:  Michael L Dustin
Journal:  Nat Immunol       Date:  2011-10-19       Impact factor: 25.606

Review 6.  Highlights of 10 years of immunology in Nature Reviews Immunology.

Authors:  Ruslan Medzhitov; Ethan M Shevach; Giorgio Trinchieri; Andrew L Mellor; David H Munn; Siamon Gordon; Peter Libby; Göran K Hansson; Ken Shortman; Chen Dong; Dmitry Gabrilovich; Leona Gabryšová; Ashleigh Howes; Anne O'Garra
Journal:  Nat Rev Immunol       Date:  2011-09-23       Impact factor: 53.106

7.  Can TNF-α boost regulatory T cells?

Authors:  Angelina M Bilate; Juan J Lafaille
Journal:  J Clin Invest       Date:  2010-11-22       Impact factor: 14.808

8.  Scaffold protein Disc large homolog 1 is required for T-cell receptor-induced activation of regulatory T-cell function.

Authors:  Alexandra Zanin-Zhorov; Jiqiang Lin; Jose Scher; Sudha Kumari; David Blair; Keli L Hippen; Bruce R Blazar; Steven B Abramson; Juan J Lafaille; Michael L Dustin
Journal:  Proc Natl Acad Sci U S A       Date:  2012-01-17       Impact factor: 11.205

9.  A simple twist of phosphate: Immunological synapse formation and T cell receptor signaling outcome in regulatory T cells.

Authors:  Talal A Chatila; Raffaele De Palma
Journal:  Eur J Immunol       Date:  2017-12       Impact factor: 5.532

Review 10.  Ubiquitous points of control over regulatory T cells.

Authors:  Fan Pan; Joseph Barbi
Journal:  J Mol Med (Berl)       Date:  2014-04-29       Impact factor: 4.599
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