title: IFN regulatory factors 4 and 8 expression in the NOD mouse.
abstract: Dendritic cells (DCs) contribute to islet inflammation and its progression to diabetes in NOD mouse model and human. DCs play a crucial role in the presentation of autoantigen and activation of diabetogenic T cells, and IRF4 and IRF8 are crucial genes involved in the development of DCs. We have therefore investigated the expression of these genes in splenic DCs during diabetes progression in NOD mice. We found that IRF4 expression was upregulated in splenocytes and in splenic CD11c(+) DCs of NOD mice as compared to BALB/c mice. In contrast, IRF8 gene expression was higher in splenocytes of NOD mice whereas its expression was similar in splenic CD11c(+) DCs of NOD and BALB/c mice. Importantly, levels of IRF4 and IRF8 expression were lower in tolerogenic bone marrow derived DCs (BMDCs) generated with GM-CSF as compared to immunogenic BMDCs generated with GM-CSF and IL-4. Analysis of splenic DCs subsets indicated that high expression of IRF4 was associated with increased levels of CD4(+)CD8α(-)IRF4(+)CD11c(+) DCs but not CD4(-)CD8α(+)IRF8(+)CD11c(+) DCs in NOD mice. Our results showed that IRF4 expression was up-regulated in NOD mice and correlated with the increased levels of CD4(+)CD8α(-) DCs, suggesting that IRF4 may be involved in abnormal DC functions in type 1 diabetes in NOD mice.
authors.affiliation: Department of Pediatric, Immunology Division, Faculty of Medicine and Health Sciences, University of Sherbrooke, 3001 12th Avenue North, Sherbrooke, QC, Canada.
authors.forename: Gilles
authors.initials: G
authors.lastname: Besin
authors.forename: Simon
authors.initials: S
authors.lastname: Gaudreau
authors.forename: Emilie
authors.initials: E
authors.lastname: Dumont-Blanchette
authors.forename: Michael
authors.initials: M
authors.lastname: Ménard
authors.forename: Chantal
authors.initials: C
authors.lastname: Guindi
authors.forename: Gilles
authors.initials: G
authors.lastname: Dupuis
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Amrani
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000235:genetics* / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D015854:Up-Regulation; D000099185:Interferon Regulatory Factor-8; D000099218:Interferon Regulatory Factor-4
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D050835:Interferon Regulatory Factors; D015847:Interleukin-4; D000099185:Interferon Regulatory Factor-8; D000099218:Interferon Regulatory Factor-4