Staff

YOKOI YukiSpecially Appointed Assistant Professor

Laboratory
Laboratory of Innate Immunity
Research Theme
Elucidation of mechanisms in mucosal immunue system centered on Paneth cells by live imaging
Research Keywords

Mucosal immunity, Innate immunity, Paneth cell, Stem cell, α-defensin, Intestinal microbiota, Intestinal environment, Cell-cell communication, Live imaging, Lifestyle disease, Inflammatory bowel disease, Preventive medicine, Food and health

Overview of Research

The intestine regulates elimination and symbiosis of luminal contents strictly by the mucosal immunity, killing pathogens, while absorbing nutrients necessary for life in addition to accepting resident bacteria beneficial for the host. However, mechanisms of the elimination and symbiosis maintained by intestinal epithelial cells, subepithelial immune cells, mesenchymal cells, and nerve cells orchestrating each other from sensing luminal ligands to responding in the host remain unknown.

Visualizing innate enteric immune responses induced by intestinal epithelium
I am interested in revealing molecular mechanisms of elimination and symbiosis regulated by intestinal cell-cell communication by visualization of innate immune responses utilizing confocal microscopy and two-photon microscopy, etc. Especially, focusing on Paneth cell which is a small intestinal epithelial cell lineage and secretes antimicrobial peptides, α-defensins to the intestinal lumen, I aim to clarify intercellular networks and intracellular signal transduction mechanisms from sensing luminal ligands to Paneth cell secretory responses.

Understanding homeostasis of intestinal environment centered on Paneth cells
Maintenance of the intestinal environment consisting of the host, foods, and the intestinal microbiota is important for our health. Disruption of the intestinal environment relates to various diseases such as lifestyle diseases and inflammatory bowel disease and the establishment of definitive therapeutics for these diseases remains to be achieved. By focusing on Paneth cells and their α-defensin secretion, I will understand how the intestinal homeostasis is regulated in mucosal immunity and contribute to establishing novel preventive medicine and therapeutics to overcome various diseases related to Paneth cell dysfunction.

Charge

Message

Because the intestine is a fundamental organ in multicellular organisms, I believe that studying biology in the intestine brings to understanding nature of life. In my research experiences, I am always impressed with the sophisticated mechanisms in organisms that can be seen from my own experimental results. Let’s pursue your own scientific questions together in our laboratory.

Representative Publications

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: 10.1073/pnas.2115230119.

Yokoi Y, Adachi T, Sugimoto R, Kikuchi M, Ayabe T, Nakamura K. Simultaneous real-time analysis of Paneth cell and intestinal stem cell response to interferon-γ by a novel stem cell niche tracking method. Biochem Biophys Res Commun 2021 doi:10.1016/j.bbrc.2021.01.050.

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: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 α-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.

北大研究者総覧参照
(https://researchers.general.hokudai.ac.jp/profile/ja.360b0c3758b2c094520e17560c007669.html)

Note

<Office Hour>
– Time: Anytime during the lecture period
– Place: Frontier-AMLS, 4F
Please contact in advance by E-mail.
E-mail: y.yokoi[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