DSpace university logo mark
Advanced Search
Japanese | English 

NAOSITE : Nagasaki University's Academic Output SITE > School of Medicine > Articles in academic journal >

Haploinsufficiency of interferon regulatory factor 4 strongly protects against autoimmune diabetes in NOD mice

File Description SizeFormat
Diabetologia58_2606.pdf859.74 kBAdobe PDFView/Open

Title: Haploinsufficiency of interferon regulatory factor 4 strongly protects against autoimmune diabetes in NOD mice
Authors: Akazawa, Satoru / Kobayashi, Masakazu / Kuriya, Genpei / Horie, Ichiro / Yu, Liping / Yamasaki, Hironori / Okita, Minoru / Nagayama, Yuji / Matsuyama, Toshifumi / Akbari, Masoud / Yui, Katsuyuki / Kawakami, Atsushi / Abiru, Norio
Issue Date: Nov-2015
Publisher: Springer Verlag
Citation: Diabetologia, 58(11), pp.2606-2614; 2015
Abstract: Aims/hypothesis: Interferon regulatory factor (IRF)4 plays a critical role in lymphoid development and the regulation of immune responses. Genetic deletion of IRF4 has been shown to suppress autoimmune disease in several mouse models, but its role in autoimmune diabetes in NOD mice remains unknown. Methods: To address the role of IRF4 in the pathogenesis of autoimmune diabetes in NOD mice, we generated IRF4-knockout NOD mice and investigated the impact of the genetic deletion of IRF4 on diabetes, insulitis and insulin autoantibody; the effector function of T cells in vivo and in vitro; and the proportion of dendritic cell subsets. Results: Heterozygous IRF4-deficient NOD mice maintained the number and phenotype of T cells at levels similar to NOD mice. However, diabetes and autoantibody production were completely suppressed in both heterozygous and homozygous IRF4-deficient NOD mice. The level of insulitis was strongly suppressed in both heterozygous and homozygous IRF4-deficient mice, with minimal insulitis observed in heterozygous mice. An adoptive transfer study revealed that IRF4 deficiency conferred disease resistance in a gene-dose-dependent manner in recipient NOD/severe combined immunodeficiency mice. Furthermore, the proportion of migratory dendritic cells in lymph nodes was reduced in heterozygous and homozygous IRF4-deficient NOD mice in an IRF4 dose-dependent manner. These results suggest that the levels of IRF4 in T cells and dendritic cells are important for the pathogenesis of diabetes in NOD mice. Conclusions/interpretation: Haploinsufficiency of IRF4 halted disease development in NOD mice. Our findings suggest that an IRF4-targeted strategy might be useful for modulating autoimmunity in type 1 diabetes.
Keywords: Autoimmunity / Dendritic cells / Interferon regulatory factor 4 / NOD mice / T cells / Type 1 diabetes
URI: http://hdl.handle.net/10069/35990
ISSN: 0012186X
DOI: 10.1007/s00125-015-3724-3
Rights: © 2015, Springer-Verlag Berlin Heidelberg. / The final publication is available at link.springer.com
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/35990

All items in NAOSITE are protected by copyright, with all rights reserved.


Valid XHTML 1.0! Copyright © 2006-2015 Nagasaki University Library - Feedback Powerd by DSpace