Kyushu University [Yoshihiro Eriguchi (Assistant Professor) Kyushu University Hospital, Department of Clinical Immunology and Rheumatology / Infectious Disease]

Yoshihiro Eriguchi

Last modified date：2023.06.21

Assistant Professor / Department of Clinical Immunology and Rheumatology / Infectious Disease
Kyushu University Hospital

1 Research Interests

2 Academic Activities

2.1 Papers

2.2 Presentations

3 Membership in Academic Society

Homepage

https://kyushu-u.pure.elsevier.com/en/persons/yoshihiro-eriguchi
　Reseacher Profiling Tool　Kyushu University Pure

Phone

092-642-5228

Fax

092-642-5247

Academic Degree

PhD. MD.

Country of degree conferring institution (Overseas)

Field of Specialization

gastroenterology, infectious disease

ORCID(Open Researcher and Contributor ID)

0000-0002-5803-230X

Total Priod of education and research career in the foreign country

06years05months

Research

Research Interests

intestinal GVHD, intestinal flora, gut immnuity
keyword : intestinal GVHD, intestinal flora, gut immnuity
2006.04～2012.12.

Academic Activities

Papers

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Yoshihiro Eriguchi, Kiminori Nakamura, Yuki Yokoi, Rina Sugimoto, Shuichiro Takahashi, Daigo Hashimoto, Takanori Teshima, Tokiyoshi Ayabe, Michael E. Selsted, André J. Ouellette, Essential role of IFN-γ in T cell-associated intestinal inflammation, JCI Insight, 10.1172/jci.insight.121886, 3, 18, 2018.09, Paneth cells contribute to small intestinal homeostasis by secreting antimicrobial peptides and constituting the intestinal stem cell (ISC) niche. Certain T cell-mediated enteropathies are characterized by extensive Paneth cell depletion coincident with mucosal destruction and dysbiosis. In this study, mechanisms of intestinal crypt injury have been investigated by characterizing responses of mouse intestinal organoids (enteroids) in coculture with mouse T lymphocytes. Activated T cells induced enteroid damage, reduced Paneth cell and Lgr5+ ISC mRNA levels, and induced Paneth cell death through a caspase-3/7-dependent mechanism. IFN-γ mediated these effects, because IFN-γ receptor-null enteroids were unaffected by activated T cells. In mice, administration of IFN-γ induced enteropathy with crypt hyperplasia, villus shortening, Paneth cell depletion, and modified ISC marker expression. IFN-γ exacerbated radiation enteritis, which was ameliorated by treatment with a selective JAK1/2 inhibitor. Thus, IFN-γ induced Paneth cell death and impaired regeneration of small intestinal epithelium in vivo, suggesting that IFN-γ may be a useful target for treating defective mucosal regeneration in enteric inflammation..

Yoshihiro Eriguchi, Shuichiro Takashima, Hideyo Oka, Sonoko Shimoji, Kiminori Nakamura, Hidetaka Uryu, Shinji Shimoda, Hiromi Iwasaki, Nobuyuki Shimono, Tokiyoshi Ayabe, Koichi Akashi, and Takanori Teshima, Graft-versus-host disease disrupts intestinal microbial ecology by inhibiting Paneth cell production of α-defensins
, Blood, doi:10.1182/blood-2011-12-401166, 120, 1, 223-231, 2012.07, 同種造血幹細胞移植は様々な血液疾患に対して根治的な治療方法である。移植片対宿主病（Graft-versus-host disease ：GVHD）と感染症は、この造血幹細胞移植の厄介な合併症であり、GVHDと感染症は互いに影響を与えていると推測されている。本研究では、GVHDと感染症の相互関係をマウスモデルにより解析した。
　αディフェンシンは、病原菌に対し殺菌活性があり、共生菌に対しては活性を有さない選択的抗菌活性を持った抗菌ペプチドである。Paneth細胞は、このαディフェンシンを分泌することにより腸内細菌叢を制御している。我々は、Paneth細胞がGVHDの標的となり、腸管でのαディフェンシンの発現が減少することを発見した。
　腸内細菌叢の分子生物学的解析では、GVHD発症マウスで腸内細菌叢の多様性が減少する一方で、正常細菌叢では0.1％にも満たず、敗血症の病因となる大腸菌が異常増殖することを示した。この細菌叢の変化は、GVHD発症マウスにのみみられ、移植前処置である放射線照射による腸管障害とは無関係であり、菌叢の変化の度合いはGVHDの重症度と有意に相関した。また、大腸菌に抗菌活性のあるポリミキシンBの経口投与は、大腸菌の異常増殖を抑え、GVHDを軽減した。
　これらの結果は、GVHD発症により正常腸内細菌叢から、病原菌が爆発的に増加した異常細菌叢へと変移する新規のメカニズムと、今まで認識されていなかったGVHDと同種造血幹細胞移植後に発症する感染症との関連を明らかにした。
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Presentations

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1.	Eriguchi Y, Nakamura K, Yokoi Y, Ayabe T, Selsted ME, and Ouellette AJ, Interferon-γ Induces Paneth Cell Loss in Mouse Ileum Enteroid Cultures. , Antimicrobial Peptides Gordon Research Conference, 2017.02.
2.	Graft-versus-host disease disrupts intestinal microbial ecology by inhibiting production of enteric defensins..

Membership in Academic Society

The Japanese Society of Internal Medicine
The Japanese Society of Gastroenterology
Japan Gastroenterological Endoscopy Society
The Japanese Association for Infectious Diseases
Japanese Association for Acute Medicine
Japanese Society of Chemotherapy

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