SNPs upstream of the minimal promoter control IL-2 expression and are candidates for the autoimmune disease-susceptibility locus Aod2/Idd3/Eae3

Genes and Immunity
Roxana Del RioCory Teuscher

Abstract

IL-2, a T-cell growth and differentiation factor, plays an important role in immune homeostasis. Previously, we identified IL2 as a candidate for Aod2, a quantitative trait locus (QTL) controlling susceptibility to autoimmune ovarian dysgenesis (AOD) induced by day 3 neonatal thymectomy. Here, we report the identification of single-nucleotide polymorphisms (SNPs) in a region upstream of the minimal IL2 promoter (-2.8 kb to -300 bp), which distinguish AOD-susceptible A/J and AOD-resistant C57BL/6J (B6/J) mice. Six of the SNPs (-1010 C --> T, -962 C --> T, -926/-925 Delta Delta --> AC, -921 T --> C, -914 T --> C and -674 G --> A) contribute to the enhanced transcriptional activity of the extended B6/J promoter relative to A/J. Importantly, the -1010 SNP resides within a canonical AP-1-binding motif with the C --> T transition at this site abrogating AP-1 binding. Moreover, these SNPs segregate with differential production of IL-2 by CD4(+) T cells as well as susceptibility alleles at Idd3 and Eae3, QTL controlling insulin-dependent diabetes mellitus and experimental allergic encephalomyelitis. These are the first SNPs identified within the extended murine IL2 promoter that control differential IL-2 transcription in CD4(+) T cells...Continue Reading

References

Sep 1, 1984·Annales d'immunologie·P de FaucalJ P Soulillou
Nov 1, 1994·International Immunology·E A Elliott, R A Flavell
Jan 1, 1993·Mammalian Genome : Official Journal of the International Mammalian Genome Society·K ChesnutE K Wakeland
Mar 1, 1996·Molecular and Cellular Biology·M Rincon, R A Flavell
Aug 1, 1996·The Journal of Experimental Medicine·M AsanoS Sakaguchi
Aug 12, 1999·Mammalian Genome : Official Journal of the International Mammalian Genome Society·N D MeekerC Teuscher
Mar 10, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·E E SolomouG C Tsokos
Aug 30, 2001·Journal of Neuroimmunology·F MatesanzA Alcina
Jul 3, 2002·The Journal of Experimental Medicine·Sean DiehlMercedes Rincón
Jul 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Randall J RoperCory Teuscher
Jun 10, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Randall J RoperCory Teuscher
May 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Angela M ThorntonEthan M Shevach
Mar 9, 2005·The Journal of Experimental Medicine·Allison L BayerThomas R Malek
Oct 18, 2005·Nature Immunology·Jason D FontenotAlexander Y Rudensky
Jan 25, 2006·Autoimmunity Reviews·Christina G Katsiari, George C Tsokos
Feb 6, 2007·Nature Genetics·Jun YamanouchiPere Santamaria
Jul 31, 2007·The New England Journal of Medicine·UNKNOWN International Multiple Sclerosis Genetics ConsortiumStephen L Hauser

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Citations

Sep 10, 2008·Journal of Clinical Immunology·Calliope A Dendrou, Linda S Wicker
Jun 25, 2009·Proceedings of the National Academy of Sciences of the United States of America·Masahito KamanakaRichard A Flavell
Apr 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Karen WheelerKenneth S K Tung
May 19, 2009·Seminars in Immunology·Jinguo WangPere Santamaria
Nov 17, 2009·Cellular Immunology·Laure K CaseCory Teuscher
Oct 2, 2013·Journal of Reproductive Immunology·Claudia RivalKenneth Tung
Jun 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Karen M SpachCory Teuscher
Feb 26, 2021·Oncogene·Ethan L MorganAndrew Macdonald

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