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Haploinsufficiency of interferon regulatory factor 4 strongly protects against autoimmune diabetes in NOD mice
http://hdl.handle.net/10069/35990
http://hdl.handle.net/10069/35990e9297f90-ca80-4030-b09b-fbe110dbf88e
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
Diabetologia58_2606.pdf (880.4 kB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2016-12-01 | |||||
| タイトル | ||||||
| タイトル | Haploinsufficiency of interferon regulatory factor 4 strongly protects against autoimmune diabetes in NOD mice | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Autoimmunity | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Dendritic cells | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Interferon regulatory factor 4 | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | NOD mice | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | T cells | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Type 1 diabetes | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| 著者 |
Akazawa, Satoru
× 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 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | 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. | |||||
| 書誌情報 |
Diabetologia 巻 58, 号 11, p. 2606-2614, 発行日 2015-11 |
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| 出版者 | ||||||
| 出版者 | Springer Verlag | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0012186X | |||||
| EISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 14320428 | |||||
| DOI | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1007/s00125-015-3724-3 | |||||
| 権利 | ||||||
| 権利情報 | c 2015, Springer-Verlag Berlin Heidelberg. | |||||
| 権利 | ||||||
| 権利情報 | The final publication is available at link.springer.com | |||||
| 著者版フラグ | ||||||
| 出版タイプ | AM | |||||
| 出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
| 引用 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Diabetologia, 58(11), pp.2606-2614; 2015 | |||||
