IL-12 plays a pathologic role at the inflammatory loci in the development of diabetes in NOD mice

Yoshio Nitta, Shunsuke Kawamoto, Fumi Tashiro, Hiroyuki Aihara, Takayuki Yoshimoto, Hideo Nariuchi, Koichi Tabayashi, Jun Ichi Miyazaki

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Accumulating evidence suggests that CD4+ T helper type 1 (Th1) cells play a major role in the development of insulin-dependent diabetes mellitus (IDDM) in the non-obese diabetic (NOD) mouse model. Interleukin (IL)-12 is a potent immunoregulatory molecule that is a key determinant of T-cell differentiation into Th1 cells, and has been implicated in the development of IDDM. To investigate the role of IL-12 that is locally produced by islet-infiltrating cells in the development of IDDM, we generated transgenic NOD mice in which the IL-12 p40 homodimer, a natural antagonist of IL-12, was produced exclusively in islets without affecting the levels of IL-12 p40 in the systemic circulation. We found that the incidence of diabetes was significantly reduced in these transgenic mice. These results clearly demonstrate that IL-12 locally produced by islet-infiltrating cells plays a critical role in the development of IDDM.

Original languageEnglish
Pages (from-to)97-104
Number of pages8
JournalJournal of Autoimmunity
Volume16
Issue number2
DOIs
Publication statusPublished - 2001 Jan 1

Keywords

  • Antagonist
  • Antoimmunity
  • Cytokine
  • T helper type 1
  • Transgenic mouse

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Nitta, Y., Kawamoto, S., Tashiro, F., Aihara, H., Yoshimoto, T., Nariuchi, H., Tabayashi, K., & Miyazaki, J. I. (2001). IL-12 plays a pathologic role at the inflammatory loci in the development of diabetes in NOD mice. Journal of Autoimmunity, 16(2), 97-104. https://doi.org/10.1006/jaut.2000.0469