Staff

OHIRA ShuyaSpecially Appointed Assistant Professor

Laboratory
Laboratory of Innate Immunity
Research Theme
Elucidating mechanisms of intestinal mucosal immune regulation mediated by Paneth cell α-defensin via intestinal microbiota
Research Keywords

Mucosal immunity, Innate immunity, Paneth cell, α-defensin, Intestinal microbiota, Systemic immunity, Inter-organ communication, Chronic inflammation, Non-communicable diseases

Overview of Research

Unraveling mechanisms of mucosal immune regulation originating from the small intestine
The intestine, composed of small and large intestines, is a multifunctional organ responsible for digestion, nutrient absorption, immune function, and various other physiological processes. Mucosal immunity in the gut is characterized by its ability to tolerate beneficial commensal microbes and dietary antigens while eliminating pathogens and potentially harmful resident bacteria. Although the intestinal microbiota has been identified as a key environmental factor influencing intestinal mucosal immunity, the mechanisms underlying mucosal immune regulation and its impact on systemic metabolism and immunity in distant organs such as the liver and pancreas remain poorly understood.
To address this, our research focuses on α-defensin, an antimicrobial peptide secreted by Paneth cells, which are uniquely located in the small intestine. We aim to clarify how α-defensin regulates mucosal immunity by selectively shaping the microbial communities in both the small and large intestines, thereby contributing to maintaining host health. Our ultimate goal is to provide new preventive and therapeutic strategies for non-communicable diseases such as diabetes and cancer that are associated with an imbalance of the intestinal microbiota.

Charge

Message

Immunity is a system that accepts what is beneficial to the host while eliminating what is harmful, serving as a fundamental mechanism that supports homeostasis and has evolved for organisms to adapt to their environment. Among the various immune-related sites, the intestine stands as the “frontline,” constantly exposed to external stimuli. Intestinal mucosal immunity, with its dynamic balance of tolerance and elimination, offers a uniquely fascinating research field. We welcome those who are eager to question, explore, and discover together with us.

Representative Publications

Yokoi Y, Nakamura R, Ohira S, Takemi S, Ayabe T, Nakamura K. Potential consequences of phototoxicity on cell function during live imaging of intestinal organoids. PLOS ONE 2024. doi.org/10.1371/journal.pone.0313213.

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.

Ohira S, Yokoi Y, Ayabe T, Nakamura K. Efficient and simple genetic engineering of enteroids using mouse isolated crypts for investigating intestinal functions. Biochem Biophys Res Commun 2022. doi.org/10.1016/j.bbrc.2022.11.008.

Kamioka M, Goto Y, Nakamura K, Yokoi Y, Sugimoto R, Ohira S, Kurashima Y, Umemoto S, Sato S, Kunisawa J, Takahashi Y, Domino SE, Renauld JC, Nakae S, Iwakura Y, Ernst PB, Ayabe T, Kiyono H. Intestinal commensal microbiota and cytokines regulate Fut2 + Paneth cells for gut defense. Proc Natl Acad Sci U S A 2022. doi.org/10.1073/pnas.2115230119.

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.org/10.1038/s41598-021-89308-y.

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 Sci Alliance 2020. doi.org/10.26508/lsa.201900592.

Nakamura K, Yokoi Y, Fukaya R, Ohira S, Shinozaki R, Nishida T, Kikuchi M, Ayabe T. Expression and Localization of Paneth Cells and Their α-Defensins in the Small Intestine of Adult Mouse. Front Immunol 2020. doi.org/10.3389/fimmu.2020.570296.

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: s.ohira[at]sci.hokudai.ac.jp

Affiliation