Immunomodulation of antigen presenting cells promotes natural regulatory T cells that prevent autoimmune diabetes in NOD mice.

PloS One
Martin J RicherM S Horwitz

Abstract

Progression towards type 1 diabetes (T1D) in susceptible patients is linked to a progressive decline in the capacity of regulatory T cells (Treg) to maintain tolerance. As such, therapies aimed at redressing the failing Treg compartment have been the subject of intense investigation. Treg dysfunction in T1D has recently been linked to a reduced capacity of antigen presenting cells (APCs) to maintain Treg function rather than Treg intrinsic defects. This suggests that therapies aimed simply at addressing the failing Treg compartment are unlikely to provide long-term protection. Here, we demonstrate that modulation of the inflammatory status of CD11b+CD11c- APCs favors the upregulation of protective Tregs in a mouse model of T1D. We further demonstrate that reduced expression of the costimulatory molecule CD40 plays a role in this increased immunoregulatory capacity. Strikingly, Treg upregulation resulted exclusively from an increase in natural Tregs rather than the peripheral conversion of conventional T cells. This suggests that modulation of CD11b+ CD11c- APCs inflammatory properties favors the establishment of natural Treg responses that, unlike adaptive Treg responses, are likely to maintain tolerance to a broad range of ant...Continue Reading

References

May 1, 1976·The Journal of Experimental Medicine·S R WebbS Kibrick
Feb 13, 1996·Annals of the New York Academy of Sciences·Y H Chen, H L Weiner
Dec 21, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·A KumanogohH Kikutani
Oct 10, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·X ZhangH L Weiner
Jan 10, 2002·The Journal of Clinical Investigation·Marc S HorwitzNora Sarvetnick
Jan 18, 2003·Science·Chandrashekhar Pasare, Ruslan Medzhitov
Feb 20, 2003·Diabetes/metabolism Research and Reviews·Hee-Sook Jun, Ji-Won Yoon
Jul 9, 2003·The Journal of Experimental Medicine·Alan D SalamaSamia J Khoury
Sep 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Qizhi TangJeffrey A Bluestone
Oct 8, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Silvia GregoriLuciano Adorini
Mar 9, 2004·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Marc S HorwitzNora Sarvetnick
Apr 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Massimo C FantiniMarkus F Neurath
Jun 9, 2004·The Journal of Experimental Medicine·Ann E HermanChristophe Benoist
Oct 7, 2004·European Journal of Immunology·Qizhi TangJeffrey A Bluestone
Dec 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Randal K GreggHabib Zaghouani
Feb 1, 2005·European Journal of Immunology·Cristiana GuiducciMario P Colombo
Mar 18, 2005·Annual Review of Immunology·Mark S Anderson, Jeffrey A Bluestone
Mar 23, 2005·Immunity·Jason D FontenotAlexander Y Rudensky
Oct 26, 2005·Nature Immunology·Karsten KretschmerHarald von Boehmer
Nov 23, 2005·The Journal of Experimental Medicine·Zhibin ChenChristophe Benoist
Sep 12, 2006·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Martin J RicherMarc S Horwitz
Nov 30, 2006·Annals of the New York Academy of Sciences·Mohamed M Jahromi, George S Eisenbarth
Jan 5, 2007·Viral Immunology·Marc S HorwitzNora Sarvetnick
Aug 7, 2007·Nature Medicine·Martin S WeberScott S Zamvil
May 30, 2008·Frontiers in Bioscience : a Journal and Virtual Library·Martin Joseph Richer, Marc Steven Horwitz
Oct 14, 2008·Expert Opinion on Biological Therapy·Lucy S K Walker
Nov 20, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ana C AndersonVijay K Kuchroo
Nov 28, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Yulan JinJin-Xiong She
Dec 17, 2008·Proceedings of the National Academy of Sciences of the United States of America·Anna Morena D'AliseDiane Mathis
May 12, 2009·Immunological Reviews·Hélène Bour-Jordan, Jeffrey A Bluestone
May 12, 2009·Immunological Reviews·Mandy L Ford, Christian P Larsen
May 30, 2009·The Journal of Clinical Investigation·Christophe M FilippiMatthias G von Herrath

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Citations

Feb 20, 2015·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·T ChenM C Poznansky
Dec 18, 2015·PloS One·Duncheng WangMark D Scott

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Methods Mentioned

BETA
transgenic
flow cytometry
ELISA

Software Mentioned

Prism GraphPad
FCAP

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