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Role of regulatory B cells in chronic intestinal inflammation: association with pathogenesis of Crohn's disease

Research Project

Project/Area Number 23590942
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionShimane University

Principal Investigator

ISHIHARA Shyunji  島根大学, 医学部, 准教授 (80263531)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords制御性B細胞 / 炎症性腸疾患 / 自然免疫 / IL-10 / クローン病モデルマウス
Research Abstract

The role of regulatory B cells (Bregs) producing IL-10 in the pathogenesis of Crohn's diseases (CD) remains unknown. We investigated IL-10 production in B cells from CD patients, as well as immunoregulatory functions of Bregs in experimental colitis mouse models. CpG DNA-induced IL-10 production was decreased in B cells from CD patients, as compared to those from healthy controls, while Bregs were found to be enriched in a population of CD19(hi)and CD1d(hi) B cells isolated from both human and mouse samples. The severity of intestinal inflammation was increased in the Breg-depleted mice, with similar results also found in adoptive transfer colitis model mice even after regulatory T cells (Tregs) depletion. Our findings show that Bregs reduced experimental colitis regardless of the presence or absence of Tregs. These results suggest that a deficiency or decrease of Bregs function exacerbates intestinal inflammation, which may be associated with the pathogenesis of CD.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (41 results)

All 2014 2013 2012 2011 Other

All Journal Article (13 results) (of which Peer Reviewed: 8 results) Presentation (28 results)

  • [Journal Article] Role of regulatory B cells in chronic intestinal inflammation: association with pathogenesis of Crohn's disease2014

    • Author(s)
      Oka A, Ishihara S, Mishima Y, Tada Y, Kusunoki R, Fukuba N, Yuki T, Kawashima K, Matsumoto S, Kinoshita Y
    • Journal Title

      Inflamm Bowel Dis

      Volume: 20 Issue: 2 Pages: 315-28

    • DOI

      10.1097/01.mib.0000437983.14544.d5

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Development of diffuse alopecia with psoriasis-like eruption during the administration of infliximab for Crohn’s disease2013

    • Author(s)
      Kawashima K, Ishihara S, Yamamoto A, Ohno Y, Fukuda K, Onishi K, Kinoshita Y
    • Journal Title

      Inflamm Bowel Dis

      Volume: 19 Issue: 3 Pages: E33-E34

    • DOI

      10.1002/ibd.22922

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pathogenesis of irritable bowel syndrome - review regarding associated infection and immune activation2013

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

      Digestion

      Volume: 87 Issue: 3 Pages: 204-11

    • DOI

      10.1159/000350054

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Butyric acid attenuates intestinal inflammation in murine DSS-induced colitis model via milk fat globule-EGF factor 82013

    • Author(s)
      Mishiro T, Kusunoki R, Otani A, Ansary M, Tongu M, Harashima N, Yamada T, Sato S, Amano Y, Itoh K, Ishihara S, Kinoshita Y
    • Journal Title

      Lab Invest

      Volume: 93 Issue: 7 Pages: 834-43

    • DOI

      10.1038/labinvest.2013.70

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Successful use of maintenance infliximab for nephropathy in a patient with secondary amyloidosis complicating Crohn's disease2013

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

      Intern Med

      Volume: 52 Pages: 1899-902

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ulcerative colitis associated with isolated unilateral hypoglossal nerve palsy2012

    • Author(s)
      Kawashima K, Ishihara S, Doi K, Uemura Y, Ohno Y, Fukuda K, Onishi K, Tada Y, Oka A, Kusunoki R, Fukuba N, Yuki T, Kinoshita Y
    • Journal Title

      Intern Med

      Volume: 51 Pages: 3135-7

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Roles of milk fat globule-epidermal growth factor 8 in intestinal inflammation2012

    • Author(s)
      Kusunoki R, Ishihara S, Aziz M, Oka A, Tada Y, Kinoshita Y
    • Journal Title

      Digestion

      Volume: 85 Issue: 2 Pages: 103-7

    • DOI

      10.1159/000334679

    • Related Report
      2013 Final Research Report 2012 Research-status Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intrarectal administration of milk fat globule epidermal growth factor-8 protein ameliorates murine experimental colitis2012

    • Author(s)
      Otani A, Ishihara S, Aziz MM, Oshima N, Mishima Y, Moriyama I, Yuki T, Amano Y, Ansary MM, Kinoshita Y
    • Journal Title

      Int J Mol Med

      Volume: 29 Pages: 349-56

    • DOI

      10.3892/ijmm.2011.866

    • Related Report
      2013 Final Research Report 2012 Research-status Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] 炎症性腸疾患における制御性B 細胞の役割2012

    • Author(s)
      岡 明彦, 石原俊治, 木下芳一
    • Journal Title

      G.I.Research

      Volume: 20 Pages: 479-485

    • Related Report
      2013 Final Research Report
  • [Journal Article] 炎症性腸疾患における制御性B細胞の役割2012

    • Author(s)
      岡 明彦、石原俊治、木下芳一
    • Journal Title

      G.I.Research

      Volume: 20 Pages: 479-485

    • Related Report
      2012 Research-status Report
  • [Journal Article] Rare case of Takayasu's arteritis associated with Crohn's disease2011

    • Author(s)
      Kusunoki R, Ishihara S, Sato M, Sumita Y, Mishima Y, Okada M, Tada Y, Oka A, Fukuba N, Oshima N, Moriyama I, Yuki T, Sato S, Amano Y, Murakawa Y, Kinoshita Y
    • Journal Title

      Intern Med

      Volume: 50 Pages: 1581-5

    • Related Report
      2013 Final Research Report
  • [Journal Article] Autophagy is required for toll-like receptor-mediated interleukin-8 production in intestinal epithelial cells2011

    • Author(s)
      Li YY, Ishihara S, Aziz MM, Oka A, Kusunoki R, Tada Y, Yuki T, Amano Y, Ansary MU, Kinoshita Y
    • Journal Title

      Int J Mol Med

      Volume: 27 Issue: 3 Pages: 337-44

    • DOI

      10.3892/ijmm.2011.596

    • Related Report
      2013 Final Research Report
  • [Journal Article] 制御性B 細胞からみたIBD 治療へのアプローチ2011

    • Author(s)
      岡明彦, 石原俊治, 木下芳一
    • Journal Title

      IBD Research

      Volume: 5 Pages: 259-64

    • Related Report
      2013 Final Research Report
  • [Presentation] Susceptibility for colitis-associated cancer development in SAMP1/Yit mice2013

    • Author(s)
      Ishihara S Tada Y, Fukuba N, Sonoyama H, Oka A, Kusunoki R, Oshima N, Moriyama I, Yuki T, Kawashima K, Kushiyama Y, Fujishiro H, Kinoshita Y
    • Organizer
      United European Gastroenterology Week (UEGW)
    • Place of Presentation
      Berlin (International Congress Centrum (ICC Berlin)), Germany
    • Year and Date
      2013-10-16
    • Related Report
      2013 Final Research Report
  • [Presentation] Eelevated matrix metalloproteinase-3 Levels in serum correlated with Crohn's disease severity: efficacy as clinical biomarker2013

    • Author(s)
      Kawashima K, Ishihara S, Sonoyama H, Tada Y, Oka A, Kusunoki R, Fukuba N, Oshima N, Moriyama I, Yuki T, Kinoshita Y
    • Organizer
      United European Gastroenterology Week (UEGW)
    • Place of Presentation
      Berlin (International Congress Centrum (ICC Berlin)), Germany
    • Year and Date
      2013-10-15
    • Related Report
      2013 Final Research Report
  • [Presentation] Down-regulation of serotonin reuptake transporter gene expression in colonic mucosa during inflammation and healing phases of inflammatory bowel disease2012

    • Author(s)
      Tada Y, Ishihara S, Kinoshita Y
    • Organizer
      United European Gastroenterology Week (UEGW)
    • Place of Presentation
      Amsterdam (Amsterdam RAI), Netherlands
    • Year and Date
      2012-10-23
    • Related Report
      2013 Final Research Report
  • [Presentation] Effects of pH-dependent release formulation of mesalazine on active ulcerative colitis resistant to time-dependent release formulation of mesalazine2012

    • Author(s)
      Kawashima K, Ishihara S, Oka A, Fukuba N, Ryusaku K, Tada Y, Tamagawa Y, Yuki T, Moriyama I, Yuki T, Kinoshita Y
    • Organizer
      United European Gastroenterology Week (UEGW)
    • Place of Presentation
      Amsterdam (Amsterdam RAI), Netherlands
    • Year and Date
      2012-10-23
    • Related Report
      2013 Final Research Report
  • [Presentation] Regulatory role of CD19highCD1dhigh B cells in intestinal inflammation: association with pathogenesis of Crohn's disease2012

    • Author(s)
      Oka A, Ishihara S, Sonoyama H, Tada Y, A.U. Mesbah, Fukuba N, Moriyama I, Yuki T, Kawashima K, Kinoshita Y
    • Organizer
      United European Gastroenterology Week (UEGW)
    • Place of Presentation
      Amsterdam (Amsterdam RAI), Netherlands
    • Year and Date
      2012-10-22
    • Related Report
      2013 Final Research Report
  • [Presentation] 制御性B細胞による腸管免疫抑制機構とその破綻による腸炎発症機序の解明-クローン病モデルマウスの病態解析からの知見とその応用-2011

    • Author(s)
      ○岡明彦、石原俊治、木下芳一
    • Organizer
      第53回日本消化器病学会大会:シンポジウム"消化器疾患と免疫"
    • Place of Presentation
      福岡国際センター他(福岡市)
    • Related Report
      2011 Research-status Report
  • [Presentation] クローン病モデルマウスのT細胞に対する制御性B細胞の影響2011

    • Author(s)
      ○岡明彦、石原俊治、多田育賢、楠龍策、福庭暢彦、森山一郎、結城崇史、天野祐二、木下芳一
    • Organizer
      第53回日本消化器病学会大会
    • Place of Presentation
      福岡国際センター他(福岡市)
    • Related Report
      2011 Research-status Report
  • [Presentation] Elevated serum pancreatic enzymes in inflammatory bowel disease associated with clinical parameters

    • Author(s)
      Sonoyama H, Kawashima K, Ishihara S, Tada Y, Oka A, Kusunoki R, Fukuba N, Oshima N, Moriyama I, Yuki T, Kinoshita Y
    • Organizer
      The 1 st Annual Meeting of Asian Organization for Crohn’s & Colitis
    • Place of Presentation
      Hotel Laforet Tokyo(Tokyo, Japan)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Milk fat globule-epidermal growth factor 8 accelerates angiogenesis-related gene expression in colonic mucosa during regenerating phase of colitis

    • Author(s)
      Tada Y, Ishihara S, Kusunoki R, Fukuba N, Sonoyama H, Oka A, Moriyama I, Yuki T, Kawashima K, Ansary MM, Kinoshita Y
    • Organizer
      United European Gastroenterology Week (UEGW)
    • Place of Presentation
      Messe Berlin (Berlin, Germany)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Televated matrix metalloproteinase-3 Levels in serum correlated with Crohn’s disease severity: efficacy as clinical biomarker

    • Author(s)
      Kawashima K, Ishihara S, Sonoyama H, Tada Y, Oka A, Kusunoki R, Fukuba N, Oshima N, Moriyama I, Yuki T, Kinoshita Y
    • Organizer
      United European Gastroenterology Week (UEGW)
    • Place of Presentation
      Messe Berlin (Berlin, Germany)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Prevalence of irritable bowel syndrome-like symptoms in ulcerative colitis patients with clinical and endoscopic evidence of remission: prospective multicenter study

    • Author(s)
      Fukuba N, Ishihara S Tada Y, Sonoyama H, Oka A, Kusunoki R, Oshima N, Moriyama I, Yuki T, Kawashima K, Kushiyama Y, Fujishiro H, Kinoshita Y
    • Organizer
      United European Gastroenterology Week (UEGW)
    • Place of Presentation
      Messe Berlin (Berlin, Germany)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Role of milk fat globule-epidermal growth factor 8 during Citrobacter rodentium-induced colitis in mice

    • Author(s)
      Oshima N, Ishihara S, Sonoyama H, Tada Y, Oka A, Kusunoki R, Fukuba N, Moriyama I, Yuki T, Kawashima K, Ansary MM, Kinoshita Y
    • Organizer
      United European Gastroenterology Week (UEGW)
    • Place of Presentation
      Messe Berlin (Berlin, Germany)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Susceptibility for colitis-associated cancer development in SAMP1/Yit mice

    • Author(s)
      Ishihara S Tada Y, Fukuba N, Sonoyama H, Oka A, Kusunoki R, Oshima N, Moriyama I, Yuki T, Kawashima K, Kushiyama Y, Fujishiro H, Kinoshita Y
    • Organizer
      United European Gastroenterology Week (UEGW)
    • Place of Presentation
      Messe Berlin (Berlin, Germany)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 潰瘍性大腸炎患者における血清マトリックスメタロプロテイナーゼ-3の疾患活動性マーカーとしての有用性の検討

    • Author(s)
      川島耕作,石原俊治,園山浩紀,多田育賢,岡 明彦,楠 龍策,福庭暢彦,大嶋直樹,結城崇史,木下芳一
    • Organizer
      第21回日本消化器関連学会週間 JDD 2013
    • Place of Presentation
      グランドプリンスホテル新高輪(東京)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 炎症性腸疾患の膵酵素異常についての臨床的検討

    • Author(s)
      園山浩紀,川島耕作,石原俊治,多田育賢,岡 明彦,楠 龍策,福庭暢彦,大嶋直樹,森山一郎,結城崇史,木下芳一
    • Organizer
      第21回日本消化器関連学会週間(JDD 2013)
    • Place of Presentation
      グランドプリンスホテル新高輪(東京)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Down-regulation of serotonin reuptake transporter gene expression in colonic mucosa during inflammation and healing phases of inflammatory bowel disease

    • Author(s)
      Tada Y, Ishihara S, Kinoshita Y
    • Organizer
      United European Gastroenterology Week (UEGW)
    • Place of Presentation
      Amsterdam, The Netherlands
    • Related Report
      2012 Research-status Report
  • [Presentation] Role of milk fat globule-epidermal growth factor 8 in intestinal inflammation and carcinogenesis

    • Author(s)
      Kusunoki R, Ishihara S, Sonoyama H, et al
    • Organizer
      United European Gastroenterology Week (UEGW)
    • Place of Presentation
      Amsterdam, The Netherlands
    • Related Report
      2012 Research-status Report
  • [Presentation] Regulatory role of CD19highCD1dhigh B cells in intestinal inflammation: association with pathogenesis of Crohn’s disease

    • Author(s)
      Oka A, Ishihara S, Sonoyama H, et al
    • Organizer
      United European Gastroenterology Week (UEGW)
    • Place of Presentation
      Amsterdam, The Netherlands
    • Related Report
      2012 Research-status Report
  • [Presentation] Expression profiles of angiogenesis- and inflammation-related genes in colonic mucosa of ulcerative colitis in remission - comparison with narrow-band imaging magnifying colonoscopy findings

    • Author(s)
      Yuki T, Ishihara S, Sonoyama H, et al
    • Organizer
      United European Gastroenterology Week (UEGW)
    • Place of Presentation
      Amsterdam, The Netherlands
    • Related Report
      2012 Research-status Report
  • [Presentation] Effects of pH-dependent release formulation of mesalazine on active ulcerative colitis resistant to time-dependent release formulation of mesalazine.

    • Author(s)
      Kawashima K, Ishihara S, Oka A, et al
    • Organizer
      United European Gastroenterology Week (UEGW)
    • Place of Presentation
      Amsterdam, The Netherlands
    • Related Report
      2012 Research-status Report
  • [Presentation] 活動期潰瘍性大腸炎に対するpH依存性メサラジン製剤の治療効果

    • Author(s)
      川島耕作,石原俊治,結城崇史,他
    • Organizer
      第98回日本消化器病学会総会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Related Report
      2012 Research-status Report
  • [Presentation] 緩解期潰瘍性大腸炎粘膜におけるNBI拡大所見と局所炎症所見および血管新生因子の対比

    • Author(s)
      結城崇史,石原俊治,多田育賢,他
    • Organizer
      第98回日本消化器病学会総会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Related Report
      2012 Research-status Report
  • [Presentation] 寛解期潰瘍性大腸炎患者IBS様症状と内視鏡像についての多施設共同研究

    • Author(s)
      福庭暢彦,石原俊治,多田育賢,他
    • Organizer
      第98回日本消化器病学会総会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Related Report
      2012 Research-status Report
  • [Presentation] 潰瘍性大腸炎の大腸粘膜におけるセロトニン取り込みトランスポーターの発現に関する検討

    • Author(s)
      多田育賢,石原俊治,楠 龍策,他
    • Organizer
      第98回日本消化器病学会総会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Related Report
      2012 Research-status Report
  • [Presentation] MFG-E8の大腸炎症および発癌への関与

    • Author(s)
      楠 龍策,石原俊治,多田育賢,他
    • Organizer
      第54回日本消化器病学会大会
    • Place of Presentation
      神戸国際展示場(神戸市)
    • Related Report
      2012 Research-status Report
  • [Presentation] 難治性潰瘍性大腸炎に対するタクロリムスによる寛解導入治療症例の経過

    • Author(s)
      結城崇史,石原俊治,多田育賢,他
    • Organizer
      第54回日本消化器病学会大会
    • Place of Presentation
      神戸国際展示場(神戸市)
    • Related Report
      2012 Research-status Report
  • [Presentation] 制御性B細胞による腸炎抑制効果 制御生T細胞非依存的な抑制機構の検討

    • Author(s)
      岡 明彦,石原俊治,多田育賢,他
    • Organizer
      第54回日本消化器病学会大会
    • Place of Presentation
      神戸国際展示場(神戸市)
    • Related Report
      2012 Research-status Report
  • [Presentation] シンポジウム14 腸管炎症におけるserotonin reuptake transporterの遺伝子発現と機能性消化管障害の病態への関与

    • Author(s)
      多田育賢,石原俊治,木下芳一
    • Organizer
      54回日本消化器病学会大会
    • Place of Presentation
      神戸国際展示場(神戸市)
    • Related Report
      2012 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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