Expression profile of peripheral tissue antigen genes in medullary thymic epithelial cells (mTECs) is dependent on mRNA levels of autoimmune regulator (Aire)

Immunobiology
Ernna H OliveiraGeraldo A Passos

Abstract

In the thymus of non-obese diabetic (NOD) mice, the expression of the autoimmune regulator (Aire) gene varies with age, and its down-regulation in young mice precedes the later emergence of type 1 diabetes mellitus (T1D). In addition, the insulin (Ins2) peripheral tissue antigen (PTA) gene, which is Aire-dependent, is also deregulated in these mice. Based in these findings, we hypothesized that the imbalance in PTA gene expression in the thymus can be associated with slight variations in Aire transcript levels. To test this, we used siRNA to knockdown Aire by in vivo electro-transfection of the thymus of BALB/c mice. The efficiency of the electro-transfection was monitored by assessing the presence of irrelevant Cy3-labeled siRNA in the thymic stroma. Importantly, Aire-siRNA reached medullary thymic epithelial cells (mTECs) down-regulating Aire. As expected, the in vivo Aire knockdown was partial and transient; the maximum 59% inhibition occurred in 48 h. The Aire knockdown was sufficient to down-regulate PTA genes; however, surprisingly, several others, including Ins2, were up-regulated. The modulation of these genes after in vivo Aire knockdown was comparable to that observed in NOD mice before the emergence of T1D. The in vi...Continue Reading

References

Jun 1, 1992·The Journal of Experimental Medicine·T MizuochiK Hirokawa
Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·M B EisenD Botstein
Mar 14, 2000·Current Opinion in Immunology·L Klein, B Kyewski
Aug 15, 2000·Journal of Cellular Physiology·C C WerneckP A Mourão
Jan 17, 2002·Journal of Immunological Methods·D H D GrayR L Boyd
Feb 21, 2002·Human Molecular Genetics·Chris RamseyLeena Peltonen
Feb 22, 2003·Genes and Immunity·J Pitkänen, P Peterson
Sep 3, 2004·Nature Reviews. Immunology·Bruno Kyewski, Jens Derbinski
Oct 20, 2004·The Journal of Experimental Medicine·Adrian ListonChristopher C Goodnow
Mar 26, 2005·Immunological Reviews·Jennifer VillaseñorDiane Mathis
Jun 29, 2005·The Journal of Experimental Medicine·Jens DerbinskiBruno Kyewski
Sep 21, 2005·The Journal of Experimental Medicine·Wenyu JiangChristophe Benoist
Nov 22, 2005·Clinical & Developmental Immunology·Lara E PereiraAftab A Ansari
Jan 25, 2006·Autoimmunity Reviews·M RizziF Indiveri
Feb 24, 2006·Nature Reviews. Immunology·Yousuke Takahama
Mar 23, 2006·Annual Review of Immunology·Bruno Kyewski, Ludger Klein
Dec 13, 2006·Clinical & Developmental Immunology·Danielle A R MagalhãesGeraldo A S Passos
Feb 17, 2007·Nature Immunology·Georg A Holländer
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Irina GavanescuDiane Mathis
Jun 9, 2007·Trends in Immunology·Mickie H ChengMark S Anderson
Jun 30, 2007·Molecular Immunology·Vivian KontPärt Peterson
Jul 21, 2007·Nature Reviews. Immunology·Diane Mathis, Christophe Benoist
May 1, 2008·PloS One·Magali IrlaCatherine Nguyen
Oct 7, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jennifer VillaseñorDiane Mathis
Dec 17, 2008·Annals of the New York Academy of Sciences·Lars-Oliver TykocinskiBruno Kyewski
Mar 24, 2009·Annual Review of Immunology·Diane Mathis, Christophe Benoist
Jun 3, 2009·The Journal of Experimental Medicine·Mireia Guerau-de-ArellanoDiane Mathis
Nov 26, 2009·Nature Reviews. Immunology·Ludger KleinBruno Kyewski
Jan 21, 2010·Cell·Bruno Kyewski, Pärt Peterson
Jan 21, 2010·Cell·Jakub AbramsonDiane Mathis
Mar 17, 2010·Biochemical and Biophysical Research Communications·Bin GuMing Zhang
Oct 23, 2010·Proceedings of the National Academy of Sciences of the United States of America·Lars-Oliver TykocinskiBruno Kyewski
Nov 17, 2010·Immunology and Cell Biology·Ruth T Taniguchi, Mark S Anderson
Nov 26, 2010·Nature Reviews. Endocrinology·Eitan M AkiravKevan C Herold
Dec 18, 2010·Current Opinion in Immunology·Mark S Anderson, Maureen A Su
Apr 15, 2011·Immunological Reviews·Todd C Metzger, Mark S Anderson
May 26, 2011·European Journal of Human Genetics : EJHG·Jessica X ChongCarole Ober
Jan 1, 2011·Frontiers in Immunology·Dina Danso-AbeamAdrian Liston

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Citations

Mar 29, 2014·BioMed Research International·Lina SunYong Zhao
Feb 2, 2013·Cancer Research·Meng-Lei ZhuMaureen A Su
Feb 26, 2016·Molecular and Cellular Endocrinology·María Teresa JuliánManel Puig-Domingo
Mar 22, 2016·The Journal of Clinical Investigation·Nadine DraginSonia Berrih-Aknin
Apr 14, 2019·Science Immunology·Joel SngEric Meffre
Feb 28, 2018·Frontiers in Immunology·Roberto Perniola
Sep 27, 2018·Journal of Immunology Research·Bingjie ZhaoWei Yang

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