Linking the circadian rhythm gene Arntl2 to interleukin 21 expression in type 1 diabetes

  1. Ute C. Rogner1
  1. 1 Institut Pasteur, CNRS URA 2578, Laboratoire de Génétique Moléculaire Murine, rue du Docteur Roux, 75015 Paris, France
  2. 2 Université Pierre et Marie Curie, Cellule Pasteur UPMC, rue du Docteur Roux, 75015 Paris, France
  1. Corresponding Author: Ute C. Rogner, Email: ute-christine.rogner{at}


The circadian rhythm related Arntl2 gene has been identified as a candidate gene for the murine type 1 diabetes locus Idd6.3. Previous studies suggested a role in expansion of CD4+CD25- T cells and by this leading to an imbalance between T effector and CD4+CD25+ T regulator cells. Our transciptome analyses identify the interleukin 21 gene as a direct target of ARNTL2. ARNTL2 binds in an allele-specific manner to the RNA polymerase binding site of the Il21 promoter and inhibits its expression in NOD.C3H congenic mice carrying C3H alleles at Idd6.3. IL21 is known to promote T cell expansion and in agreement with these findings mice with C3H alleles at Idd6.3 produce lower numbers of CD4+IL21+ and CD4+ and CD8+ T cells compared to mice with NOD alleles at Idd6.3. Our results describe a novel and rather unexpected role for Arntl2 in the immune system that lies outside of its predicted function in the circadian rhythm regulation.

  • Received November 6, 2013.
  • Accepted January 29, 2014.

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