The circadian gene Arntl2 on distal mouse chromosome 6 controls thymocyte apoptosis - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Mammalian Genome Année : 2017

The circadian gene Arntl2 on distal mouse chromosome 6 controls thymocyte apoptosis

Résumé

Nonobese diabetic (NOD) mice are a model for type 1 diabetes that displays defects in central immune tolerance, including impairment of thymocyte apoptosis and proliferation. Thymocyte apoptosis is decreased in NOD/Lt mice compared to nondiabetic C3H/HeJ and C57BL/6 mice. Analysis of a set of NOD.C3H and NOD.B6 congenic mouse strains for distal chromosome 6 localizes the phenotype to the 700 kb Idd6.3 interval. Idd6.3 contains the type 1 diabetes candidate gene aryl hydrocarbon receptor nuclear translocator-like 2 (Arntl2), encoding a circadian rhythm-related transcription factor. Newly generated Arntl2 -/- mouse strains reveal that inactivation of the B6 allele of Arntl2 is sufficient to both decrease thymocyte apoptosis and proliferation. When expressed from C3H or B6 alleles, ARNTL2 inhibits the transcription of interleukin 21 (Il21), a major player in the regulation of immune responses. IL-21 injection abolishes the B6 allele-mediated decrease of apoptosis and proliferation. Interestingly, IL-21 also leads to an increase in thymic proinflammatory Th17 helper cells. Our results identify Arntl2 as a gene controlling thymocyte apoptosis and proliferation along with Th17 development through the IL-21 pathway.
Fichier principal
Vignette du fichier
10.1007_s00335-016-9665-4.pdf (3.14 Mo) Télécharger le fichier
Origine : Publication financée par une institution

Dates et versions

hal-03051465 , version 1 (10-12-2020)

Identifiants

Citer

Basile Lebailly, Francina Langa, Christian Boitard, Philip Avner, Ute Christine Rogner. The circadian gene Arntl2 on distal mouse chromosome 6 controls thymocyte apoptosis. Mammalian Genome, 2017, 28 (1-2), pp.1-12. ⟨10.1007/s00335-016-9665-4⟩. ⟨hal-03051465⟩
18 Consultations
127 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More