Journal of Gastroenterology

, Volume 40, Issue 1, pp 16–23

MyD88-deficient mice develop severe intestinal inflammation in dextran sodium sulfate colitis

  • Akihiro Araki
  • Takanori Kanai
  • Takahiro Ishikura
  • Shin Makita
  • Koji Uraushihara
  • Ryoichi Iiyama
  • Teruji Totsuka
  • Kiyoshi Takeda
  • Shizuo Akira
  • Mamoru Watanabe
Article

DOI: 10.1007/s00535-004-1492-9

Cite this article as:
Araki, A., Kanai, T., Ishikura, T. et al. J Gastroenterol (2005) 40: 16. doi:10.1007/s00535-004-1492-9

Abstract

Background

Gut commensal microbes affect the development and activation of the mucosal and systemic immune systems. However, the exact molecular mechanism of these microbes that is involved in the development of colitis remains unclear.

Methods

The present study was conducted to determine the distinct role of the innate immune system in the development of a dextran sulfate sodium (DSS) colitis model in MyD88−/− mice, because myeloid differentiation protein (MyD88) is a major adaptor molecule essential for signaling via Toll-like receptors (TLRs). To this end, MyD88−/− and wild-type (WT) mice received sterile distilled water containing 1.2% DSS for 8 days. The survival rate, total clinical score (body weight loss, stool consistency, and rectal bleeding), colon length, and histological score were assessed. The expression of surface markers (F4/80 and CD4) on infiltrating lamina propria mononuclear cells was analyzed immunohistochemistrically.

Results

MyD88−/− mice exhibited increased susceptibility to DSS-induced colitis, as reflected by significantly higher lethality and higher clinical and histological scores, and more severe colonic shortening compared to WT mice. Immunohistochemical analysis revealed a significant increase of both F4/80+ macrophages and CD4+ T cells in the inflamed mucosa in DSS-fed MyD88−/− mice compared to DSS-fed WT mice.

Conclusions

These findings suggest that, via MyD88 signaling, the innate immune system in the gut plays an important protective role in colitis.

Key words

luminal bacterial florainflammationinnate immune systemMyD88DSS-induced colitis

Copyright information

© Springer-Verlag Tokyo 2005

Authors and Affiliations

  • Akihiro Araki
    • 1
  • Takanori Kanai
    • 1
  • Takahiro Ishikura
    • 1
  • Shin Makita
    • 1
  • Koji Uraushihara
    • 1
  • Ryoichi Iiyama
    • 1
  • Teruji Totsuka
    • 1
  • Kiyoshi Takeda
    • 2
  • Shizuo Akira
    • 2
  • Mamoru Watanabe
    • 1
  1. 1.Department of Gastroenterology and Hepatology, Graduate SchoolTokyo Medical and Dental UniversityTokyoJapan
  2. 2.Department of Host Defense, Research Institute for Microbial DiseasesOsaka UniversityOsakaJapan