title: Linking the circadian rhythm gene Arntl2 to interleukin 21 expression in type 1 diabetes.
abstract: The circadian rhythm-related aryl hydrocarbon receptor nuclear translocator-like 2 (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 this then creates an imbalance in the ratio between T-effector and CD4(+)CD25(+) T-regulator cells. Our transcriptome analyses identify the interleukin 21 (IL21) gene (Il21) 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 with 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 circadian rhythm regulation.
authors: Department of Developmental & Stem Cells Biology, Institut Pasteur, CNRS URA 2578, Laboratoire de Génétique Moléculaire Murine, Paris, FranceUniversité Pierre et Marie Curie, Cellule Pasteur UPMC, Paris, France.
authors: Basile
authors: B
authors: Lebailly
authors: Department of Developmental & Stem Cells Biology, Institut Pasteur, CNRS URA 2578, Laboratoire de Génétique Moléculaire Murine, Paris, France.
authors: Chenxia
authors: C
authors: He
authors: Department of Developmental & Stem Cells Biology, Institut Pasteur, CNRS URA 2578, Laboratoire de Génétique Moléculaire Murine, Paris, France ute-christine.rogner@pasteur.fr.
authors: Ute C
authors: UC
authors: Rogner
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D002940:Circadian Rhythm / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008809:Mice, Inbred C3H; D016688:Mice, Inbred NOD; D034741:RNA, Small Interfering / Q000235:genetics; D000098546:Interleukin-21
chemical_list: D056930:ARNTL Transcription Factors; C431792:Arntl2 protein, mouse; D007378:Interleukins; D034741:RNA, Small Interfering; D000098546:Interleukin-21