An N-terminal mutation of the Foxp3 transcription factor alleviates arthritis but exacerbates diabetes.

Immunity
Jaime DarceChristophe Benoist

Abstract

Maintenance of lymphoid homeostasis in a number of immunological and inflammatory contexts is served by a variety of regulatory T (Treg) cell subtypes and depends on interaction of the transcription factor FoxP3 with specific transcriptional cofactors. We report that a commonly used insertional mutant of FoxP3 (GFP-Foxp3) modified its molecular interactions, blocking HIF-1α but increasing IRF4 interactions. The transcriptional profile of these Treg cells was subtly altered, with an overrepresentation of IRF4-dependent transcripts. In keeping with IRF4-dependent function of Treg cells to preferentially suppress T cell help to B cells and Th2 and Th17 cell-type differentiation, GFP-FoxP3 mice showed a divergent susceptibility to autoimmune disease: protection against antibody-mediated arthritis in the K/BxN model, but greater susceptibility to diabetes on the NOD background. Thus, specific subfunctions of Treg cells and the immune diseases they regulate can be influenced by FoxP3's molecular interactions, which result in divergent immunoregulation.

References

May 26, 1995·Science·J D KatzD Mathis
Nov 29, 1996·Cell·V KouskoffD Mathis
Mar 23, 2005·Immunity·Jason D FontenotAlexander Y Rudensky
Jun 4, 2005·Arthritis and Rheumatism·Koichiro OhmuraChristophe Benoist
Mar 23, 2006·Annual Review of Immunology·Steven F Ziegler
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Bin LiMark I Greene
Jun 21, 2008·Nature Reviews. Immunology·Dario A A VignaliCreg J Workman
Sep 19, 2008·Nature Immunology·Tracy S P HengUNKNOWN Immunological Genome Project Consortium
Jun 19, 2009·Nature Immunology·Markus FeuererChristophe Benoist
Sep 22, 2009·Immunity·Michael J Barnes, Fiona Powrie
Oct 3, 2009·Science·Ashutosh ChaudhryAlexander Y Rudensky
Dec 4, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jonathan P JacobsDiane Mathis
Mar 17, 2010·Proceedings of the National Academy of Sciences of the United States of America·Markus FeuererChristophe Benoist
Sep 28, 2010·Current Opinion in Immunology·Yan XiaoMark I Greene
Jan 27, 2011·Nature Reviews. Immunology·Daniel J Campbell, Meghan A Koch
Jun 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Martin A KriegelDiane Mathis

❮ Previous
Next ❯

Citations

Aug 28, 2012·Nature Immunology·Dipayan RudraAlexander Y Rudensky
Sep 21, 2013·Nature Immunology·Dalia BurzynDiane Mathis
Oct 13, 2012·Nature Reviews. Immunology·Kenneth J Oestreich, Amy S Weinmann
Sep 19, 2012·Proceedings of the National Academy of Sciences of the United States of America·Eric T ClambeyHolger K Eltzschig
Apr 12, 2013·Proceedings of the National Academy of Sciences of the United States of America·Ricardo S PaivaJocelyne Demengeot
Aug 13, 2013·Proceedings of the National Academy of Sciences of the United States of America·Ayla ErgunUNKNOWN ImmGen Consortium
Jan 25, 2013·Open Biology·Stephanie M CoomesMark S Wilson
Jan 3, 2013·The Journal of Clinical Investigation·Ruan ZhangLaurence A Turka
Aug 11, 2012·PloS One·Sonja SchallenbergKarsten Kretschmer
Jan 1, 2014·The Journal of Experimental Medicine·Kate S SmigielDaniel J Campbell
Feb 19, 2013·International Immunopharmacology·Zuojia ChenBin Li
Mar 13, 2014·Proceedings of the National Academy of Sciences of the United States of America·Alessandra FerraroChristophe Benoist
Apr 30, 2014·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Fan Pan, Joseph Barbi
Aug 28, 2014·European Journal of Immunology·Cathleen PetzoldKarsten Kretschmer
Aug 25, 2015·Molecular Immunology·Anthony T Phan, Ananda W Goldrath
Nov 5, 2014·Immunity·Asis PalazonRandall S Johnson
Mar 29, 2013·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·X ChenL Wang
Jul 1, 2014·European Journal of Immunology·Xiufen ChenJustin Kline
Apr 10, 2014·Immunological Reviews·Joseph BarbiFan Pan
Jul 22, 2014·European Journal of Immunology·Christian T MayerTim Sparwasser
Jun 19, 2015·Immunological Reviews·Joseph BarbiFan Pan
Feb 17, 2015·Scandinavian Journal of Immunology·R ElhageD Klatzmann
May 22, 2013·Journal of Diabetes Research·Cathleen PetzoldKarsten Kretschmer
May 29, 2012·Immunity·Talal A Chatila, Calvin B Williams
Feb 20, 2015·Nature Communications·Huey-Wen HsiaoMing-Zong Lai
May 27, 2016·Nature Reviews. Rheumatology·Ursula FearonDouglas J Veale
Jul 14, 2016·Proceedings of the National Academy of Sciences of the United States of America·Baihao ZhangTasuku Honjo
Jun 15, 2018·Journal of Leukocyte Biology·Tzu-Sheng Hsu, Ming-Zong Lai
Sep 12, 2017·Nature Immunology·Ho-Keun KwonChristophe Benoist
Dec 23, 2017·Proceedings of the National Academy of Sciences of the United States of America·Ho-Keun KwonChristophe Benoist
Aug 2, 2017·Nature Reviews. Immunology·Ling LuFan Pan
Nov 16, 2019·European Journal of Immunology·José Almeida-SantosJocelyne Demengeot

❮ Previous
Next ❯

Related Concepts

Related Feeds

B cells: Gene Expression

B lymphocytes are white blood cells that play a role in the adaptive immune system by secreting antibodies. Here is the latest research on gene expression in B cells.

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.

Autoimmune Diabetes & Tolerance

Patients with type I diabetes lack insulin-producing beta cells due to the loss of immunological tolerance and autoimmune disease. Discover the latest research on targeting tolerance to prevent diabetes.

Autoimmune Polyendocrinopathies

Autoimmune polyendocrinopathies, also called polyglandular autoimmune syndromes (PGASs), or polyendocrine autoimmune syndromes(PASs), are a heterogeneous group of rare diseases characterized by autoimmune activity against more than one endocrine organ, although non-endocrine organs can be affected. Discover the latest research on autoimmune polyendocrinopathies here.