• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Elucidation of a novel mechanism leading regulatory B cells dysfunction of in Crohn's disease

Research Project

Project/Area Number 18K07971
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionShimane University

Principal Investigator

Ishihara Shunji  島根大学, 学術研究院医学・看護学系, 教授 (80263531)

Co-Investigator(Kenkyū-buntansha) 三島 義之  島根大学, 学術研究院医学・看護学系, 助教 (30397864)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords制御性B細胞 / ATP / クローン病 / 潰瘍性大腸炎 / IL-10 / 自然免疫 / Crohn病 / アデノシン三リン酸 / 腸管免疫 / P2X7受容体 / アデノシン三リン酸(ATP)
Outline of Final Research Achievements

Regulatory B cells (Breg) dysfunction is associated with the pathogenesis of Crohn's disease (CD), but its mechanism is unknown. We focused on extracellular adenosine triphosphate (ATP) produced in colitis tissues and examined its effect on Breg dysfunction in CD patients.
B cells isolated from the spleen of mice were cultured and various concentration of ATP was added to the culture system. The effect of ATP on IL-10 induced by various bacterial antigens was examined, showing that IL-10 production by B cells was suppressed depending on the ATP concentration. We also examined the effect of ATP on IL-10 production by B cells isolated from the mesenteric lymph nodes of ATP receptor P2X7-deficient mice. As a result, the decrease in IL-10 production due to ATP was recovered by P2X7 receptor deficiency in B cells. Thus, ATP reduces IL-10 production via the P2X7 receptor of B cells, suggesting that this mechanism may be involved in Breg dysfunction in association with the pathogenesis of CD.

Academic Significance and Societal Importance of the Research Achievements

これまで、様々な自己免疫疾患において、CD同様にBregの機能異常が病態に関わる示されてきた。しかし各々の疾患で「なぜBregの機能が低下しているのか?」という疑問を解明する研究はおこなわれていない。今回、私共が着目した「細胞外ATPによる Bregの機能減弱」に関する報告は国内外を通じて皆無である。Bregの機能低下機序を明らかにし、そのメカニズムが特異的にCDの病態に関わること、あるいは本メカニズム深く関わるCDのポピュレーションが存在すること検証できれば、本研究の成果は、これまでと異なる視点からの新知見となり、将来の新規治療開発につながっていくと思われる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (21 results)

All 2021 2020 2019 2018

All Journal Article (13 results) (of which Peer Reviewed: 12 results,  Open Access: 3 results) Presentation (8 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Intermittent Purpura Development Associated with Leukocytoclastic Vasculitis Induced by Infliximab for Crohn's Disease2021

    • Author(s)
      Kishimoto Kenichi、Kawashima Kousaku、Fukunaga Mai、Kotani Satoshi、Sonoyama Hiroki、Oka Akihiko、Mishima Yoshiyuki、Oshima Naoki、Ishimura Norihisa、Ishikawa Noriyoshi、Maruyama Riruke、Ishihara Shunji
    • Journal Title

      Internal Medicine

      Volume: 60 Issue: 3 Pages: 385-389

    • DOI

      10.2169/internalmedicine.5340-20

    • NAID

      130007979732

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2021-02-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detection and Quantification of Transforming Growth Factor-β1 Produced by Murine B Cells: Pros and Cons of Different Techniques2021

    • Author(s)
      Mishima Yoshiyuki、Oka Akihiko、Ishihara Shunji
    • Journal Title

      Methods Mol Biol.

      Volume: 2270 Pages: 113-124

    • DOI

      10.1007/978-1-0716-1237-8_7

    • ISBN
      9781071612361, 9781071612378
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential gene expression analysis of dasatinib-induced colitis in a patient with chronic myeloid leukemia followed for 3?years: a case report2021

    • Author(s)
      Oshima Naoki、Mishima Yoshiyuki、Shibagaki Kotaro、Kawashima Kousaku、Ishimura Norihisa、Ikejiri Fumiyoshi、Onishi Chie、Okada Takahiro、Inoue Masaya、Moriyama Ichiro、Suzumiya Junji、Kinoshita Yoshikazu、Ishihara Shunji
    • Journal Title

      BMC Gastroenterology

      Volume: 21 Issue: 1 Pages: 19-19

    • DOI

      10.1186/s12876-020-01584-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Non-adherence to Medications in Pregnant Ulcerative Colitis Patients Contributes to Disease Flares and Adverse Pregnancy Outcomes2020

    • Author(s)
      Watanabe C、Nagahori M、Fujii T、Yokoyama K、Yoshimura N、Kobayashi T、Yamagami H、Kitamura K、Takashi K、Nakamura S、Naganuma M、Ishihara S、Esaki M、Yonezawa M、Kunisaki R、Sakuraba A、Kuji N、Miura S、Hibi T、Suzuki Y、Hokari R
    • Journal Title

      Digestive Diseases and Sciences

      Volume: 66 Issue: 2 Pages: 577-586

    • DOI

      10.1007/s10620-020-06221-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular Mechanisms of Microbiota-Mediated Pathology in Irritable Bowel Syndrome2020

    • Author(s)
      Mishima Yoshiyuki、Ishihara Shunji
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 22 Pages: 8664-8664

    • DOI

      10.3390/ijms21228664

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expert opinions on the current therapeutic management of inflammatory bowel disease during the COVID-19 pandemic: Japan IBD COVID-19 taskforce, intractable diseases, the health and labor sciences research.2020

    • Author(s)
      akase H, Matsumoto T, Matsuura M, Iijima H, Matsuoka K, Ohmiya N, Ishihara S, Hirai F, Wagatsuma K, Yokoyama Y, Hisamatsu T.
    • Journal Title

      Digestion

      Volume: - Issue: 5 Pages: 1-9

    • DOI

      10.1159/000510502

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ten-year follow-up study of linear immunoglobulin A dermatosis complicated with ulcerative colitis2020

    • Author(s)
      Sonoyama H, Mishima Y, Ishihara S, Oshima N, Moriyama I, Kawashima K, Chinuki Y, Morita E, Kinoshita Y
    • Journal Title

      Clin J Gastroenterol

      Volume: 13 Issue: 2 Pages: 164-169

    • DOI

      10.1007/s12328-019-01047-w

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interleukin-33 delays recovery of mucosal inflammation via downregulation of homeostatic ABCG5/8 in the colon2019

    • Author(s)
      Mishima Yoshiyuki、Sonoyama Hiroki、Ishihara Shunji、Oshima Naoki、Moriyama Ichiro、Kawashima Kousaku、Kinoshita Yoshikazu
    • Journal Title

      Laboratory Investigation

      Volume: 100 Issue: 3 Pages: 491-502

    • DOI

      10.1038/s41374-019-0329-3

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Capabilities of fecal calprotectin and blood biomarkers as surrogate endoscopic markers according to ulcerative colitis disease type2019

    • Author(s)
      Sonoyama Hiroki、Kawashima Kousaku、Ishihara Shunji、Kotani Satoshi、Fukuba Nobuhiko、Oka Akihiko、Kusunoki Ryusaku、Tada Yasumasa、Mishima Yoshiyuki、Oshima Naoki、Moriyama Ichiro、Yuki Takafumi、Onishi Koji、Kinoshita Yoshikazu
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 64 Issue: 3 Pages: 265-270

    • DOI

      10.3164/jcbn.18-92

    • NAID

      130007641427

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Capabilities of fecal calprotectin and blood biomarkers as surrogate endoscopic markers according to ulcerative colitis disease type2019

    • Author(s)
      Sonoyama H, Kawashima K, Ishihara S, Kotani S, Fukuba N, Oka A, Kusunoki R, Tada Y, Mishima Y, Oshima N, Moriyama I, Yuki T, Onishi K, Kinoshita Y
    • Journal Title

      J Clin Biochem Nutr

      Volume: in press

    • NAID

      130007641427

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 【今月のテーマ(総説)】ウステキヌマブによるクローン病の治療―有効性と安全性からみた位置付け―2019

    • Author(s)
      石原俊治、川島耕作、木下芳一
    • Journal Title

      日本消化器病学会雑誌

      Volume: 116 Pages: 216-223

    • Related Report
      2018 Research-status Report
  • [Journal Article] Serum amyloid A level correlated with endoscopic findings in patients with Crohn’s disease?Possible biomarker for evaluating mucosal healing2018

    • Author(s)
      Ishihara Shunji、Tada Yasumasa、Kawashima Kousaku、Kataoka Masatoshi、Sonoyama Hiroki、Yamashita Noritsugu、Oka Akihiko、Kusunoki Ryusaku、Fukuba Nobuhiko、Mishima Yoshiyuki、Oshima Naoki、Moriyama Ichiro、Yuki Takafumi、Kinoshita Yoshikazu
    • Journal Title

      Digestive and Liver Disease

      Volume: 50 Issue: 6 Pages: 553-558

    • DOI

      10.1016/j.dld.2017.12.010

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Irritable Bowel Syndrome-Like Symptoms in Ulcerative Colitis Patients in Clinical Remission: Association with Residual Colonic Inflammation2018

    • Author(s)
      Ishihara Shunji、Kawashima Kousaku、Fukuba Nobuhiko、Tada Yasumasa、Kotani Satoshi、Mishima Yoshiyuki、Oshima Naoki、Kinoshita Yoshikazu
    • Journal Title

      Digestion

      Volume: 99 Issue: 1 Pages: 46-51

    • DOI

      10.1159/000494412

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 高齢潰瘍性大腸炎患者に対するタクロリムス投与における腎機能障害の検討2021

    • Author(s)
      大嶋 直樹、川島 耕作、石原 俊治
    • Organizer
      第107回日本消化器病学会総会、東京
    • Related Report
      2020 Annual Research Report
  • [Presentation] 潰瘍性大腸炎の治療目標は組織学的治癒か?-長期臨床的寛解維持予測における内視鏡的完全治癒と組織学的治癒の比較検討-2020

    • Author(s)
      岡  明彦、川島 耕作、園山 浩紀、三島 義之、石原 俊治
    • Organizer
      第113回日本消化器病学会中国支部例会、山口
    • Related Report
      2020 Annual Research Report
  • [Presentation] 感染後過敏性腸症候群におけるTLR9の関与の検討2020

    • Author(s)
      三島義之,古谷聡史,川島耕作,石原俊治
    • Organizer
      第16回日本消化管学会総会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Interleukin-33 delays recovery of mucosal inflammation by down-reguation of ABCG5/8 in colon2019

    • Author(s)
      Mishima Y, Sonoyama H, Ishihara S, Oshima N, Moriyama I, Kawashima K, Kinoshita Y
    • Organizer
      DDW2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 潰瘍性大腸炎の病型別にみた粘膜治療評価における各種バイオマーカーの有用性と問題点2019

    • Author(s)
      Shibagaki K, Yuki T, Taniguchi H, Kotani S, Ishimura N, Ishihara S
    • Organizer
      第105回日本消化器病学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 便中カルプロテクチン低値は臨床的内視鏡的寛解潰瘍性大腸炎の組織学的寛解を同定し,長期的な臨床的寛解維持を予測する2019

    • Author(s)
      川島耕作,石原俊治,木下芳一
    • Organizer
      JDDW2019
    • Related Report
      2019 Research-status Report
  • [Presentation] 組織学的所見に基づいた臨床的寛解潰瘍性大腸炎患者における過敏性腸症候群様症状の頻度に関する検討2018

    • Author(s)
      川島耕作、石原俊治、福庭暢彦、片岡祐俊、山下詔嗣、園山浩紀、多田育賢、楠龍策、三島義之、大嶋直樹、結城崇史、木下芳一
    • Organizer
      第104回日本消化器病学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] pH依存型メサラジン放出調節製剤投与後に心筋炎を発症した潰瘍性大腸炎の1例.2018

    • Author(s)
      川島耕作、石原俊治、加藤輝士、片岡祐俊、古谷聡史、園山浩紀、三島義之、大嶋直樹、木下芳一
    • Organizer
      第9回日本炎症性腸疾患学会学術集会
    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi