Mechanism of hyperinflammation in chronic granulomatous disease: mouse iPS cells expressing human gp91phox

• Project/Area Number: 22791021
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: National Research Institute for Child Health and Development
• Principal Investigator: KAWAI Toshinao 独立行政法人国立成育医療研究センター, 成育遺伝研究部, 室長 (20328305)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 小児免疫 / アレルギー / 膠原病学 / 慢性肉芽腫症 / 免疫不全 / 活性酸素 / サイトカイン / 肉芽腫性腸炎 / 食細胞 / NADPHオキシダーゼ / iPS細胞

Research Abstract

We investigated an underlying mechanisms of excessive inflammation in patients with chronic granulomatous disease. Our data suggested that reactive oxygen species generated by NADPH oxidase suppressed the lipopolysaccharide-induced inflammatory cytokine production through NLRP3 inflammasome and NF_κB signaling pathway in monocytes that play a central role of immune response. Although further works are required to clarify the mechanisms of excessive inflammation in CGD patients, this data indicates that reduction of reactive oxygen species generated by NADPH oxidase would induce dysregulated production of inflammatory cytokines.

Research Products

• [Journal Article] Onodera M, et al. Thalidomide Attenuates Excessive Inflammation without Interrupting Lipopolysaccharide-driven Inflammatory Cytokine Production in Chronic Granulomatous Disease. (2013)
  • Author(s): Kawai T
  • Journal Title: Clinical Immunology Volume: 147 Issue: 2 Pages: 122-128
  • DOI: 10.1016/j.clim.2013.03.004
  • Peer Reviewed
• [Journal Article] A case of macrophage activation syndrome developing in a patient with chronic granulomatous disease-associated colitis. (2013)
  • Author(s): Akagi K, Kawai T, et al.
  • Journal Title: Journal of Pediatric Hematology/Oncology
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/23652865
  • Peer Reviewed
• [Journal Article] 食細胞の数、機能の異常症～慢性肉芽腫症と食細胞機能異常症～ (2013)
  • Author(s): 河合利尚
  • Journal Title: 小児科診療 Volume: 76 Pages: 431-437
• [Journal Article] A case of macrophage activation syndrome developing in a patient with chronic granulomatous disease-associated colitis (2013)
  • Author(s): Kazuko Akagi
  • Journal Title: Journal of Pediatric Hematology/Oncology Volume: in press
  • Peer Reviewed
• [Journal Article] 慢性肉芽腫症と他の食細胞機能異常症 (2012)
  • Author(s): 河合利尚
  • Journal Title: 小児内科 Volume: 44 Pages: 242-243
• [Journal Article] 深在性真菌症の実際 (2011)
  • Author(s): 河合利尚
  • Journal Title: 深在性真菌症 Volume: 7 Pages: 44-45
• [Journal Article] Osteomyelitis Due to Trimethoprim/Sulfamethoxazole-Resistant Edwardsiella tarda Infection in a Patient with X-linked Chronic Granulomatous Disease. (2011)
  • Author(s): Kawai T, et al.
  • Journal Title: Infection Volume: 39 Issue: 2 Pages: 171-3
  • DOI: 10.1007/s15010-011-0080-1
• [Journal Article] Osteomyelitis Due to Trimethoprim/Sulfamethoxazole-Resistant Edwardsiella tarda Infection in a Patient with X-linked Chronic Granulomatous Disease (2011)
  • Author(s): Kawai T, Kusakabe H, Seki A, Kobayashi S, Onodera M
  • Journal Title: Infection Volume: (In press)
  • Peer Reviewed
• [Journal Article] 慢性肉芽腫症 (2010)
  • Author(s): 河合利尚
  • Journal Title: 小児科診療 Volume: 73Suppl Pages: 226-228
• [Presentation] 慢性肉芽腫症の肉芽腫性疾患に対するサリドマイド治療 (2012)
  • Author(s): 河合利尚
  • Organizer: 第44回小児感染症学会
  • Place of Presentation: 北九州
  • Year and Date: 2012-11-24
• [Presentation] Foxp3-Retrovirus Transduction to CD4+ T Cells Induce Regulatory Potential with Decreased Secretion of Interferon-gamma (2012)
  • Author(s): Kawai T, et al.
  • Organizer: American Society of Gene &Cell Therapy
  • Place of Presentation: Philadelphia, PA, USA
  • Year and Date: 2012-05-16
• [Presentation] 慢性肉芽腫症腸炎に対するサリドマイド治療の効果と安全性 (2012)
  • Author(s): 河合利尚
  • Organizer: 第115回小児科学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2012-04-20
• [Presentation] Foxp3－Retrovirus Transduction to CD4+ T Cells Induce Regulatory Potential with Decreased Secretion of Interferon－gamma (2012)
  • Author(s): Toshinao Kawai
  • Organizer: American Society of Gene &Cell Therapy
  • Place of Presentation: Philadelphia, PA, USA
• [Presentation] 慢性肉芽腫症における非感染性炎症疾患の検討 (2011)
  • Author(s): 河合利尚
  • Organizer: 第114回小児科学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-08-14
• [Presentation] Gene Therapy for a Patient with Chronic Granulomatous Disease (2011)
  • Author(s): Kawai T
  • Organizer: 17回遺伝子治療学会シンポジウム
  • Place of Presentation: 九州
  • Year and Date: 2011-07-15
• [Presentation] Gene Therapy for a Patient with Chronic Granulomatous Disease (2011)
  • Author(s): 河合利尚
  • Organizer: 第17回遺伝子治療学会
  • Place of Presentation: 九州
• [Presentation] 非感染性腸炎を合併した慢性肉芽腫症の検討 (2010)
  • Author(s): 村山静子、田村英一郎、河合利尚、井田博幸
  • Organizer: 第42回小児感染症学会
  • Place of Presentation: 仙台
  • Year and Date: 2010-11-27
• [Book] 小児科診断治療指針(分担 慢性肉芽腫症) (2012)
  • Author(s): 河合利尚
  • Publisher: 中山書店
• [Book] 小児科診断治療指針（分担 慢性肉芽腫症） (2012)
  • Author(s): 河合利尚
  • Total Pages: 2
  • Publisher: 中山書店