Staff

NAKAMURA KiminoriProfessor

Laboratory
Laboratory of Innate Immunity
Research Theme
Understanding mechanisms of disease development via intestinal microbiota regulated by Paneth cell a-defensin
Research Keywords

Mucosal immunology, Innate immunity, Antimicrobial peptides, Defensin, Intestine, Paneth cell, Stem cell, Infectious disease, Inflammatory bowel disease, Gut microbiota, DOHaD

Overview of Research

Promotion of mother and child health by regulating the gut microbiota of α-defensin
Trillions of bacteria live in our gut, forming the gut microbiome, a rich ecosystem that performs various functions in our bodies. Imbalanced gut microbiota (dysbiosis) is associated with the onset of various diseases such as obesity, diabetes, and even depression and autism. DOHaD, the idea that the mother’s environment during pregnancy affects the child’s further development of diseases including obesity and diabetes, is becoming known. As an environmental factor inducing DOHaD, maternal gut microbiota affected by dietary habits has been shown to be important, but the underlying mechanisms for DOHaD are unclear. We hypothesized that maternal dysbiosis induced by decreased α-defensin via poor dietary habits would be transmitted to the gut environment of the offspring and contribute to an increased risk of future disease. Our goal is to contribute to improving mother and child health by verifying this hypothesis and further developing dietary components that can enhance α-defensins.

Development of novel therapies for inflammatory bowel disease
The number of patients with Inflammatory Bowel Disease (IBD), Crohn’s disease and ulcerative colitis, has been increasing continuously world-wide, including Japan. However, the pathogenesis is unknown and no fundamental therapeutics exist. To understand pathophysiology and pathogenesis of IBD, we analyze the roles for AMPs including -defensin, related signal molecules in Paneth cells as well as crosstalk between innate and adaptive immunity in the gut. Taken together, we are eager to contribute to improving the health of patients with IBD and infectious diseases by understanding a mechanism of innate intestinal immunity and by developing new therapeutics.

Charge

Message

If you have the motivation and idea, you have an environment where you can freely proceed with your research.We hope motivated students interested in innate immunity and intestinal microbiota to join our lab.

Representative Publications

Shimizu Y, Yamamura R, Yokoi Y, Ayabe T, Ukawa S, Nakamura K, Okada E, Imae A, Nakagawa T, Tamakoshi A, Nakamura K. Shorter sleep time relates to lower human defensin 5 secretion and compositional disturbance of the intestinal microbiota accompanied by decreased short-chain fatty acid production. Gut Microbes 2023. doi.o10.1080/19490976.2023.2190306rg/.

Nakamura S, Nakamura K, Yokoi Y, Shimizu Y, Ohira S, Hagiwara M, Song Z, Gan L, Aizawa T, Hashimoto D, Teshima T, Ouellette AJ, Ayabe T. Decreased Paneth cell α-defensins promote fibrosis in a choline-deficient L-amino acid-defined high-fat diet-induced mouse model of nonalcoholic steatohepatitis via disrupting intestinal microbiota. Sci Rep 2023. doi.org/10.1038/s41598-023-30997-y.

Suzuki K, Nakamura K, Shimizu Y, Yokoi Y, Hagiwara M, Ohira S, Wang Y, Song Y, Aizawa T, Ayabe T. Decrease of alpha-defensin impairs intestinal metabolite homeostasis via dysbiosis in mouse chronic social defeat stress model. Sci Rep 2021. doi: 10.1038/s41598-021-89308-y.

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. 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. 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.

Refer to HOKKAIDO UNIVERSITY RESEARCHERS DIRECTORY

Note

<Office Hour>
– Time: Anytime during the lecture period
– Place: Frontier-AMLS, 4F
Please contact in advance by E-mail.
E-mail: kiminori[at]sci.hokudai.ac.jp

<Related SDGs> 　
3. GOOD HEALTH AND WELL-BEING
4. QUALITY EDUCATION
9. INDUSTRY, INNOVATION AND INFRASTRUCTURE
17. PARTNERSHIPS FOR THE GOALS

Affiliation