Inhibition of type 1 diabetes by upregulation of the circadian rhythm-related aryl hydrocarbon receptor nuclear translocator-like 2.
The genetic locus Idd6 is involved in type 1 diabetes development in the non-obese diabetic (NOD) mouse through its effect on the immune system and in particular, on T cell activities. Analysis of congenic strains for Idd6 has established the Aryl hydrocarbon receptor nuclear translocator-like 2 (Arntl2) as a likely candidate gene. In this study we investigate the role of Arntl2 in the autoimmune disease and T cell activation. An Arntl2 expressing plasmid was transfected into CD4(+) T cells by nucleofection. Expression levels of cytokines and CD4(+) T cell activation markers, cell death, apoptosis, and cell proliferation rates were characterized in ex vivo experiments whilst in vivo the transfected cells were transferred into NOD.SCID mice to monitor diabetes development. The results demonstrate that Arntl2 overexpression leads to inhibition of CD4(+) T cell proliferation and decreases in their diabetogenic activity without influence on the expression levels of cytokines, CD4(+) T cell activation markers, cell death, and apoptosis. Our findings suggest that Arntl2 at the Idd6 locus may act via the inhibition of CD4(+) T cell proliferation and the reduction in the diabetogenic activity of CD4(+) T cells to protect against autoimmune type 1 diabetes in the NOD mice.
He
Chen-Xia
CX
Institut Pasteur, Unité de Génétique Moléculaire Murine, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France.
Prevot
Nicolas
N
Boitard
Christian
C
Avner
Philip
P
Rogner
Ute C
UC
D056930:ARNTL Transcription Factors / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002940:Circadian Rhythm; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010957:Plasmids; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation / Q000502:physiology*
D056930:ARNTL Transcription Factors; C431792:Arntl2 protein, mouse; D012333:RNA, Messenger