Immune tolerance. Regulatory T cells generated early in life play a distinct role in maintaining self-tolerance

Science
Siyoung YangDiane Mathis

Abstract

Aire is an important regulator of immunological tolerance, operating in a minute subset of thymic stromal cells to induce transcripts encoding peptides that guide T cell selection. Expression of Aire during a perinatal age window is necessary and sufficient to prevent the multiorgan autoimmunity characteristic of Aire-deficient mice. We report that Aire promotes the perinatal generation of a distinct compartment of Foxp3(+)CD4(+) regulatory T (Treg) cells, which stably persists in adult mice. This population has a role in maintaining self-tolerance, a transcriptome and an activation profile distinguishable from those of Tregs produced in adults. Underlying the distinct Treg populations are age-dependent, Aire-independent differences in the processing and presentation of thymic stromal-cell peptides, resulting in different T cell receptor repertoires. Our findings expand the notion of a developmentally layered immune system.

References

Nov 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·M BogueD Mathis
Dec 22, 1989·Cell·L A Herzenberg, L A Herzenberg
Sep 1, 1996·The Journal of Experimental Medicine·C KurtsH Kosaka
Jun 11, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Osami KanagawaBarbala A Vaupel
Jun 26, 2002·Proceedings of the National Academy of Sciences of the United States of America·Felix J BakerMark M Davis
Sep 29, 2004·Proceedings of the National Academy of Sciences of the United States of America·Helene C DujardinAntonio Bandeira
Mar 23, 2005·Immunity·Jason D FontenotAlexander Y Rudensky
Aug 23, 2005·Immunity·Mark S AndersonDiane Mathis
Sep 21, 2005·The Journal of Experimental Medicine·Wenyu JiangChristophe Benoist
Oct 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Zhibin ChenDiane Mathis
Dec 1, 2006·Nature Immunology·Jeong M KimAlexander Y Rudensky
Feb 3, 2007·International Immunology·Magdalena J PolanczykHalina Offner
May 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jamie WongChristophe Benoist
Nov 23, 2007·Nature·Lauren W CollisonDario A A Vignali
Dec 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Itay ShalevGary Levy
Mar 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eileen T SamyKenneth S K Tung
Aug 9, 2008·Science·James M GardnerMark S Anderson
Mar 24, 2009·Annual Review of Immunology·Diane Mathis, Christophe Benoist
Jun 3, 2009·The Journal of Experimental Medicine·Mireia Guerau-de-ArellanoDiane Mathis
Jun 19, 2009·Nature Immunology·Markus FeuererChristophe Benoist
May 1, 2010·Nature Immunology·Maria HinterbergerLudger Klein
Jul 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Andrew S KohDiane Mathis
Aug 4, 2010·The Journal of Experimental Medicine·Junko NishioChristophe Benoist
Oct 12, 2010·Science·Yuri P RubtsovAlexander Y Rudensky
May 6, 2011·Proceedings of the National Academy of Sciences of the United States of America·Anna Morena D'AliseChristophe Benoist
Dec 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Matthieu GiraudChristophe Benoist
Jan 13, 2012·Annals of the New York Academy of Sciences·Kai Kisand, Pärt Peterson
May 4, 2012·Proceedings of the National Academy of Sciences of the United States of America·Ruth T TaniguchiMark S Anderson
Mar 9, 2013·Science·Sven MalchowPeter A Savage
Sep 7, 2013·Frontiers in Immunology·Yuri O PoluektovScheherazade Sadegh-Nasseri
Jan 28, 2014·Current Opinion in Immunology·Elizabeth D Mellins, Lawrence J Stern

❮ Previous
Next ❯

Citations

Jan 31, 2016·Cellular and Molecular Life Sciences : CMLS·Takeshi Nitta, Harumi Suzuki
Jan 23, 2016·Trends in Immunology·David M RichardsMarkus Feuerer
Feb 24, 2016·The Journal of Clinical Investigation·Theo van den BroekFemke van Wijk
Jan 20, 2016·Nature Immunology·Douglas G Millar, Pamela S Ohashi
Aug 11, 2015·European Journal of Immunology·Melvin Cohn
Dec 9, 2015·European Journal of Immunology·Mitsuru Matsumoto
Sep 15, 2015·European Journal of Immunology·Uku HaljasorgPärt Peterson
Dec 29, 2015·Current Opinion in Organ Transplantation·Quan Liu, Heth R Turnquist
Jun 18, 2015·Immunity·Ari B MolofskyRichard M Locksley
Mar 15, 2016·Nature Reviews. Immunology·Mark S Anderson, Maureen A Su
Mar 20, 2016·International Immunopharmacology·Xin ChenZhiMing Huang
Mar 22, 2016·The Journal of Clinical Investigation·Pearl Bakhru, Maureen A Su
Oct 12, 2015·Current Diabetes Reports·Jeffrey D RoizenHakon Hakonarson
Mar 31, 2016·Nature Reviews. Immunology·Ming O Li, Alexander Y Rudensky
Nov 21, 2015·Immunity·Tiffany C ScharschmidtMichael D Rosenblum
Nov 19, 2015·Annals of the New York Academy of Sciences·Alice Y Chan, Mark S Anderson
Sep 16, 2015·The Journal of Experimental Medicine·Alison M PatersonArlene H Sharpe
Apr 14, 2016·Proceedings of the National Academy of Sciences of the United States of America·Katrin KlockeKajsa Wing
Aug 11, 2015·Frontiers in Immunology·Gabriel SkogbergOlov Ekwall
Jul 5, 2015·Journal of Clinical Immunology·Kai Kisand, Pärt Peterson
Jul 1, 2015·Current Opinion in Organ Transplantation·David M Rothstein, Geoffrey Camirand
Apr 19, 2016·The Journal of Clinical Investigation·Zhenke WenCornelia M Weyand
May 20, 2015·Trends in Immunology·Xudong Li, Ye Zheng
Apr 19, 2016·Immunological Reviews·Jakub Abramson, Eystein S Husebye
May 2, 2015·Science·Atsushi Tanaka, Shimon Sakaguchi
Oct 31, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Zhengxiao OuyangGang Huang
May 12, 2016·Annual Review of Immunology·Marisella PanduroDiane Mathis
Feb 26, 2016·Autoimmunity·Katherine L CrosslandDesa Lilic
Jan 13, 2016·Journal of Pediatric Gastroenterology and Nutrition·Carsten EngelmannHermann Kreyenberg
Oct 5, 2016·JCI Insight·Gaurang JhalaBalasubramanian Krishnamurthy
Aug 10, 2016·Current Opinion in Immunology·Øyvind BruserudEystein S Husebye
Sep 7, 2016·Frontiers in Pediatrics·Lucia De MartinoMariacarolina Salerno
Sep 22, 2016·Mucosal Immunology·N TorowE S Gollwitzer
Oct 21, 2015·Current Opinion in Allergy and Clinical Immunology·Annick A J M van de Ven, Klaus Warnatz
Dec 13, 2016·Nature Immunology·Yonatan HerzigJakub Abramson
Dec 20, 2016·Nature Immunology·Yohko KitagawaShimon Sakaguchi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Atlas of the Human Thymus

Examining the genomics, transcriptomics, proteomics, and metabolomics of the human thymus gland at the single cell level will help build a unique profile for each cell type and a three-dimensional map of how cell types work together to form tissues. Discover the latest research on the cell atlas of the human thymus 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.