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.
- © 2014 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.