Laboratory of Innate Immunity
- Research Theme
- Regulation of innate immunity in mucosal immunity by Paneth cell alpha-defensin / Pathogenesis of inflammatory bowel disease and lifestyle diseases
- Research Keywords
innate immunity, antimicrobial peptide, mucosal immunity, intestinal epithelial cell, Paneth cell, alpha-defensin, stem cell, intestinal microbiota, intestinal environment, inflammatory bowel disease, lifestyle diseases, food and medicine, preventive medicine, therapeutics
AYABE Tokiyoshi Professor
NAKAMURA Kiminori Associate Professor
YOKOI Yuki Specially Appointed Assistant Professor
Overview of Research and Education
Mucosal immunology serves an important role in the host defense. One goal of our laboratory is to understand molecular mechanisms that regulate function of innate immunity. Focusing on antimicrobial peptides (AMPs) as well as Paneth cells that produce and secrete those molecules, we aim to test new paradigms in the field of mucosal immunity. At the surface of intestinal epithelia, where a vast number and variety of microbes create resident intestinal microbiota, the host must deal with the microbiota as well as potential pathogens that might cause infection. α-Defensins are abundant components of Paneth cell secretory granules and secreted into the lumen in response to cholinergic or bacterial stimuli. By developing ex vivo functional assay systems using isolated intact crypts and intestinal organoids, we have been analyzing how host cells detect microbes, how AMP activation and secretion are regulated, and how microbes and intestinal epithelia such as Paneth cells crosstalk.
The number of patients with inflammatory bowel disease (IBD) as well as lifestyle diseases have been increasing continuously in world-wide, including in Japan. Finally, to understand pathophysiology and pathogenesis of IBD, Crohn’s disease and ulcerative colitis in particular and lifestyle diseases such as obesity, diabetes, and nonalcoholic steatohepatitis, we analyze roles of AMPs, related signal molecules in Paneth cells and crosstalk between innate and adaptive immunity in the gut. Taken together, we will contribute to improving quality of life of patients with IBD and lifestyle diseases by getting our knowledge of AMPs as effectors of the mucosal immunity and by developing preventive medicine and novel therapeutics.
Laboratory of Innate Immunity (pdf)
- Charge (US):
School of Science, Biological Science course (Macromolecular Functions), Core Laboratories
- Charge (GS):
Graduate School of Life Science, Division of Life Science, Transdisciplinary Life Science Course, Functional Cellular Sciences
North 21 West 11, Kita-ku, Sapporo, Hokkaido
- ayabe*sci.hokudai.ac.jp (Please replace * with @ when sending e-mail.)
Nakamura K, Yokoi Y, Fukaya R, Ohira S, Shinozaki R, Nishida T, Kikuchi M, Ayabe T. Expression and localization of Paneth cells and their alpha-defensins in the small intestine of adult mouse. Front Immunol 2020. 11: 570296. doi: 10.3389/fimmu.2020.570296.
Shimizu Y, Nakamura K, Yoshii A, Yokoi Y, Kikuchi M, Shinozaki R, Nakamura S, Ohira S, Sugimoto R, Ayabe T. Paneth cell alpha-defensin misfolding correlates with dysbiosis and ileitis in Crohn’s disease model mice. Life Science Alliance 2020. 3(6):e201900592. doi: 10.26508/lsa.201900592.
Yokoi Y, Nakamura K, Yoneda T, Kikuchi M, Sugimoto R, Shimizu Y, Ayabe T. Paneth cell granule dynamics on secretory responses to bacterial stimuli in enteroids. Sci Rep 2019. doi.org/10.1038/s41598-019-39610-7.
Takakuwa A, Nakamura K, Kikuchi M, Sugimoto R, Ohira S, Yokoi Y, Ayabe T. Butyric acid and leucine induce alpha-defensin secretion from small intestinal Paneth cells. Nutrients 2019, 11(11), 2817; doi.org/10.3390/nu11112817.
Eriguchi Y, Nakamura K, Yokoi Y, Takahashi S, Hashimoto D, Teshima T, Ayabe T, Selsted ME, Ouellette AJ. Essential role of interferon-gamma in T cell-associated intestinal inflammation. JCI Insight 2018. 3(18): e121886. doi.org/10.1172/jci.insight.121886.
Hayase E, Hashimoto D, Nakamura K, Noizat C, Ogasawara R, Takahashi S, Ohigashi H, Yokoi Y, Sugimoto R, Matsuoka S, Ara T, Yokoyama E, Yamakawa T, Ebata K, Kondo T, Hiramine R, Aizawa T, Ogura Y, Hayashi T, Mori H, Kurokawa K, Tomizuka K, Ayabe T, Teshima T., R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus-host disease., J Exp Med 2017. 214: 3507-3518.
Refer to HOKKAIDO UNIVERSITY RESEARCHERS DIRECTORY
3. GOOD HEALTH AND WELL-BEING
4. QUALITY EDUCATION
9. INDUSTRY, INNOVATION AND INFRASTRUCTURE
17. PARTNERSHIPS FOR THE GOALS