TNF downmodulates the function of human CD4+CD25hi T-regulatory cells

Blood
Xavier ValenciaPeter E Lipsky

Abstract

CD4+CD25+ T-regulatory cells (Tregs) play an essential role in maintaining immunologic homeostasis and preventing autoimmunity. However, little is known about the exogenous factors that regulate their differentiation and function. Here, we report that TNF inhibits the suppressive function of both naturally occurring CD4+CD25+ Tregs and TGFbeta1-induced CD4+CD25+ T-regulatory cells. The mechanism of this inhibition involves signaling through TNFRII that is constitutively expressed selectively on unstimulated Tregs and that is up-regulated by TNF. TNF-mediated inhibition of suppressive function is related to a decrease in FoxP3 mRNA and protein expression by the Tregs. Notably, CD4+CD25hi Tregs isolated from patients with active rheumatoid arthritis (RA) expressed reduced levels of FoxP3 mRNA and protein and poorly suppressed the proliferation and cytokine secretion of CD4+ effector T cells in vitro. Treatment with anti-TNF antibody (infliximab) increased FOXP3 mRNA and protein expression by CD4+CD25hi Tregs and restored their suppressive function. Thus, TNF has a novel action in modulating autoimmunity, by inhibiting CD4+CD25+ Treg activity.

References

Apr 24, 1987·Cell·J W KapplerP Marrack
Jan 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·M GrellP Scheurich
Nov 30, 2000·The New England Journal of Medicine·P E LipskyUNKNOWN Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group
Feb 13, 2001·The International Journal of Biochemistry & Cell Biology·H Wajant, P Scheurich
Jul 24, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·C Baecher-AllanD A Hafler
Mar 22, 2002·Nature·Xiaoming LiJonathan D Ashwell
May 30, 2002·Nature Reviews. Immunology·Marc Feldmann
Jul 3, 2002·Nature Reviews. Immunology·Ethan M Shevach
Jul 18, 2002·The Journal of Experimental Medicine·Helmut JonuleitAlexander H Enk
Aug 7, 2002·The Journal of Experimental Medicine·Francesco AnnunziatoSergio Romagnani
Sep 11, 2002·Proceedings of the National Academy of Sciences of the United States of America·Ava J WuHugh O McDevitt
Jan 18, 2003·Science·Chandrashekhar Pasare, Ruslan Medzhitov
Mar 4, 2003·Nature Immunology·Jason D FontenotAlexander Y Rudensky
Mar 4, 2003·Nature Immunology·Roli KhattriFred Ramsdell
Jun 9, 2004·The Journal of Experimental Medicine·Ann E HermanChristophe Benoist
Jul 29, 2004·Current Medicinal Chemistry·I CarpentierR Beyaert
Jul 29, 2004·The Journal of Experimental Medicine·Michael R EhrensteinClaudia Mauri
Aug 19, 2004·The Journal of Allergy and Clinical Immunology·X Dao Nguyen, Douglas S Robinson
Sep 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Edward Y Kim, Hung-Sia Teh
Oct 7, 2004·International Immunology·Haruhiko YagiShimon Sakaguchi
Oct 8, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Geoffrey L StephensEthan M Shevach
Jul 23, 2005·International Reviews of Immunology·Shimon Sakaguchi, Noriko Sakaguchi
Oct 8, 2005·The Journal of Clinical Investigation·Sarah E AllanMegan K Levings
Nov 23, 2005·The Journal of Experimental Medicine·Zhibin ChenChristophe Benoist

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Citations

Apr 27, 2012·Inflammatory Bowel Diseases·Heike Bantel, Klaus Schulze-Osthoff
Jan 12, 2010·Rheumatology International·Inger Marie SkoieRoald Omdal
Nov 6, 2008·Archives of Dermatological Research·Annegret KuhnPeter H Krammer
Sep 25, 2007·Journal of Clinical Immunology·Shomron Ben-HorinIlan Bank
Sep 17, 2008·Journal of Clinical Immunology·Yisong Y Wan, Richard A Flavell
Jul 28, 2013·Current Rheumatology Reports·Faye A H CoolesAmy E Anderson
Nov 10, 2007·Clinical Reviews in Allergy & Immunology·Gikas E KatsifisSharon M Wahl
Dec 20, 2007·Clinical Reviews in Allergy & Immunology·E Toubi
Oct 23, 2009·Clinical Immunology : the Official Journal of the Clinical Immunology Society·S SalemiR D Amelio
Nov 12, 2013·Veterinary Immunology and Immunopathology·V QeskaA Beineke
Dec 4, 2013·Expert Reviews in Molecular Medicine·Anne M Pesenacker, Lucy R Wedderburn
Oct 5, 2013·Experimental & Molecular Medicine·Su-Jin MoonMi-La Cho
May 2, 2007·Nature Clinical Practice. Rheumatology·Jagadeesh BayrySrini V Kaveri
Oct 31, 2007·Nature Clinical Practice. Rheumatology·Xavier Valencia, Peter E Lipsky
Dec 30, 2006·Nature Reviews. Drug Discovery·Vibeke StrandJohn D Isaacs
Apr 20, 2006·Nature Reviews. Immunology·Luca GattinoniNicholas P Restifo
Feb 24, 2007·Nature Reviews. Immunology·Arne N AkbarDerek C Macallan
Dec 1, 2007·Nature Reviews. Immunology·Jagadeesh BayrySrini V Kaveri
Oct 3, 2009·Nature Reviews. Rheumatology·Jonathan H EsenstenJeffrey A Bluestone
Sep 3, 2010·Nature Reviews. Rheumatology·Clare A Notley, Michael R Ehrenstein
Nov 28, 2008·Proceedings of the National Academy of Sciences of the United States of America·Fabian Flores-BorjaMichael R Ehrenstein
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Alexandra Zanin-ZhorovMichael L Dustin
Sep 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Paul A BeavisFionula M Brennan
Mar 21, 2007·The Journal of Experimental Medicine·Jessica R KocksReinhold Förster
Nov 20, 2010·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Ying ZhangZhi-yong Sheng
Jan 25, 2012·The Journal of Infectious Diseases·Danielle N Kroetz, George S Deepe
May 1, 2010·Journal of Molecular Cell Biology·Xiaohui ZhouSong Guo Zheng
May 14, 2010·Rheumatology·Ellen J WehrensBerent J Prakken
May 12, 2012·Rheumatology·Steven O'ReillyJacob M van Laar
Apr 7, 2007·Current Opinion in Rheumatology·Myew-Ling Toh, Pierre Miossec

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