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

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590942
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Shimane University
• Principal Investigator: ISHIHARA Shyunji 島根大学, 医学部, 准教授 (80263531)
• Project Period (FY): 2011 – 2013
• 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.

Research Products

• [Journal Article] Role of regulatory B cells in chronic intestinal inflammation: association with pathogenesis of Crohn's disease (2014)
  • 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 Pages: 315-28
  • DOI: 10.1097/01.MIB.0000437983.14544.d5
  • Peer Reviewed
• [Journal Article] Development of diffuse alopecia with psoriasis-like eruption during the administration of infliximab for Crohn's disease (2013)
  • Author(s): Kawashima K, Ishihara S, Yamamoto A, Ohno Y, Fukuda K, Onishi K, Kinoshita Y
  • Journal Title: Inflamm Bowel Dis Volume: 19 Pages: E33-4
  • DOI: 10.1002/ibd.22922
  • Peer Reviewed
• [Journal Article] Pathogenesis of irritable bowel syndrome - review regarding associated infection and immune activation (2013)
  • 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 Pages: 204-11
  • DOI: 10.1159/000350054
  • Peer Reviewed
• [Journal Article] Butyric acid attenuates intestinal inflammation in murine DSS-induced colitis model via milk fat globule-EGF factor 8 (2013)
  • 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 Pages: 834-43
  • DOI: 10.1038/labinvest.2013.70
  • Peer Reviewed
• [Journal Article] Successful use of maintenance infliximab for nephropathy in a patient with secondary amyloidosis complicating Crohn's disease (2013)
  • 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
  • Peer Reviewed
• [Journal Article] Ulcerative colitis associated with isolated unilateral hypoglossal nerve palsy (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Roles of milk fat globule-epidermal growth factor 8 in intestinal inflammation (2012)
  • Author(s): Kusunoki R, Ishihara S, Aziz M, Oka A, Tada Y, Kinoshita Y
  • Journal Title: Digestion Volume: 85 Pages: 103-7
  • DOI: 10.1159/000334679
  • Peer Reviewed
• [Journal Article] Intrarectal administration of milk fat globule epidermal growth factor-8 protein ameliorates murine experimental colitis (2012)
  • 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
  • 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
• [Journal Article] Rare case of Takayasu's arteritis associated with Crohn's disease (2011)
  • 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
• [Journal Article] Autophagy is required for toll-like receptor-mediated interleukin-8 production in intestinal epithelial cells (2011)
  • 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 Pages: 337-44
  • DOI: 10.3892/ijmm.2011.596
• [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
• [Presentation] Susceptibility for colitis-associated cancer development in SAMP1/Yit mice (2013)
  • 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
• [Presentation] Eelevated matrix metalloproteinase-3 Levels in serum correlated with Crohn's disease severity: efficacy as clinical biomarker (2013)
  • 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
• [Presentation] Down-regulation of serotonin reuptake transporter gene expression in colonic mucosa during inflammation and healing phases of inflammatory bowel disease (2012)
  • 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
• [Presentation] Effects of pH-dependent release formulation of mesalazine on active ulcerative colitis resistant to time-dependent release formulation of mesalazine (2012)
  • 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
• [Presentation] Regulatory role of CD19highCD1dhigh B cells in intestinal inflammation: association with pathogenesis of Crohn's disease (2012)
  • 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