Research

Involvement of innate immunity in intestinal mucosal inflammation

The Project Leader's Profile

Kiyoshi Takeda

Professor, Laboratory of Immune Regulation, Osaka University Medical School/Graduate School of Medicine

In 1992, graduated from the Osaka University, School of Medicine and obtained his M.D. In 1998, completed the doctoral course at the Graduate School of Medicine, Osaka University and obtained his Ph.D. In 1998, Research Associate in Department of Biochemistry, Hyogo College of Medicine (Hyogo, Japan). In 1999, Research Associate at Research Institute for Microbial Diseases, Osaka University (Osaka, Japan). In 2004, appointed as Professor at Medical Institute for Bioregulation, Kyushu University (Fukuoka, Japan). From 2007, he holds the current position. Specialized in immunology. He has received the 7th prize of the Japanese Society of Immunology.

Project Leader
  • Kiyoshi Takeda, M.D., Ph.D., Professor, Laboratory of Immune Regulation, Osaka University Medical School/Graduate School of Medicine
Research Members
  • Kenya Honda, Associate Professor, Laboratory of Immune Regulation, Osaka University Medical School/Graduate School of Medicine
  • Masahiro Yamamoto, Assistant Professor, Laboratory of Immune Regulation, Osaka University Medical School/Graduate School of Medicine

Summary

We previously found that mice lacking Stat3 specifically in innate immune cell populations showed abnormal activity of innate immunity and developed chronic inflammatory bowel diseases. In the absence of Stat3, IL-10-mediated suppression of innate immune cell activity is abolished, and therefore innate immune cells such as macrophages and dendritic cells are abnormally activated. In this condition, Toll-like receptors (TLR) triggers over-production of inflammatory cytokines including IL-12p40 through the recognition of microflora in the intestine, leading to development of Th1/Th17-dependent inflammatory bowed diseases. Therefore, the activity of innate immune cells residing in the intestinal lamina propria should be finely regulated to prevent excessive inflammatory responses. As one of the mechanisms, we found that the nuclear IκB protein IκBNS is selectively expressed in the innate immune cells of the intestinal lamina propria. IκBNS was found to suppress TLR-dependent induction of IL-6 and IL-12p40, and thereby limit intestinal inflammation. Thus, we are investigating the mechanisms for regulation of innate immune responses, which will lead to the understanding the pathogenesis of chronic inflammatory bowel diseases.
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Some of Recent Papers

  1. Atarashi, K., Nishimura, J., Shima, T., Umesaki, Y., Yamamoto, M., Onoue, M., Yagita, H., Ishii, N., Evans, R., Honda, K., and Takeda, K.: ATP drives lamina propria TH17 cell differentiation. Nature 455, 808-812, 2008.
  2. Kayama, H., Rairez-Carrozzi, V. R., Yamamoto, M., Mizutani, T., Kuwata, H., Iba, H., Matsumoto, M., Honda, K., Smale, S. T., and Takeda, K.: Class-specific regulation of pro-inflammatory genes by MyD88 pathways and IκBζ. J. Biol. Chem. 283, 12468-12477, 2008.
  3. Kuwata, H., Matsumoto, M., Atarashi, K., Morishita, H., Hirotani, T., Koga, R., and Takeda, K.: IκBNS inhibits induction of a subset of Toll-like receptor-dependent genes and limits inflammation. Immunity 24, 41-51, 2006.
  4. Hirotani, T., Lee, P. Y., Kuwata, H., Yamamoto, M., Matsumoto, M., Kawase, I., Akira, S., and Takeda, K.: The nuclear IκB protein IκBNS selectively inhibits lipopolysaccharide-induced IL-6 production in macrophages of the colonic lamina propria. J. Immunol. 174, 3650-3657, 2005.