Modeling and analyzing pathogenesis of cryopyrin-associated periodic syndrome using induced pluripotent stem cells

• Project/Area Number: 21890118
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: Kyoto University
• Principal Investigator: SAITO Megmu Kyoto University, iPS細胞研究所, 特定拠点助教 (90535486)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2010: ¥1,235,000 (Direct Cost: ¥950,000、Indirect Cost: ¥285,000); Fiscal Year 2009: ¥1,365,000 (Direct Cost: ¥1,050,000、Indirect Cost: ¥315,000)
• Keywords: Cryopyrin関連周期熱症候群 / NLRP3 / 疾患iPS細胞 / iPS細胞 / 血球分化

Research Abstract

Cryopyrin-associated periodic syndrome (CAPS) is an severe autoinflammatory syndrome caused by mutations of NLRP3. To investigate the mechanism of disease and for drug screening, we established patient-specific induced pluripotent stem (iPS) cells from two CAPS patients with somatic mosaicism. Both mutant and wild type clones were obtained, and these clones were differentiated into macrophages. Disease-associated features such as overproduction of IL-1beta, pyronecrosis were observed only in mutant clones. Thus we succeeded to establish a disease-model of CAPS using iPS cells.

Research Products

• [Journal Article] Inflammasomes and related diseases. (2011)
  • Author(s): (日本語)Saito MK.
  • Journal Title: Nihon Rinsho Meneki Gakkai Kaishi.(PubMed PMID : 21372510) 34(1) Pages: 20-28
  • NAID: 10029431634
• [Journal Article] インフラマソームとその関連疾患の最近の知見 (2011)
  • Author(s): 齋藤潤
  • Journal Title: 日本臨床免疫学会雑誌 Volume: 34 Pages: 20-28
  • NAID: 10029431634
• [Journal Article] Enhanced NF-κB activation with an inflammasome activator correlates with activity of autoinflammatory disease associated with NLRP3 mutations outside of exon 3 : comment on the article by Jeru et al. (2010)
  • Author(s): Kambe N, Satoh T, Tanizaki H, Fujisawa A, Saito MK, Nishikomori R.
  • Journal Title: Arthritis Rheum. 62(10) Pages: 3123-3124
• [Journal Article] The inflammasome, an innate immunity guardian, participates in skin urticarial reactions and contact hypersensitivity. (2010)
  • Author(s): Kambe N, Nakamura Y, Saito M, Nishikomori R.
  • Journal Title: Allergol Int. 59(2) Pages: 105-113
• [Journal Article] Enhanced NF-κB activation with an inflammasome activator correlates with activity of autoinflammatory disease associated with NLRP3 mutations outside of exon 3 : comment on the article by Jeru et al. (2010)
  • Author(s): Kambe N, Satoh T, Tanizaki H, Fujisawa A, Saito MK, Nishikomori R.
  • Journal Title: Arthritis Rheum. Volume: 62 Pages: 3123-3124
  • Peer Reviewed
• [Journal Article] The inflammasome, an innate immunity guardian, participates in skin urticarial reactions and contacthypersensitivity. (2010)
  • Author(s): Kambe N, Nakamura Y, Saito M, Nishikomori R.
  • Journal Title: Allergol Int. Volume: 59 Pages: 105-113
  • Peer Reviewed
• [Journal Article] Orderly hematopoietic development of induced pluripotent stem cells via Flk-1(+) hemoangiogenic progenitors. (2009)
  • Author(s): Niwa A, Umeda K, Chang H, Saito M, Okita K, Takahashi K, Nakagawa M, Yamanaka S, Nakahata T, Heike T.
  • Journal Title: J Cell Physiol. 221(2) Pages: 367-377
• [Journal Article] Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria. (2009)
  • Author(s): Nakamura Y, Kambe N, Saito M, Nishikomori R, Kim YG, Murakami M, Nunez G,Matsue H.
  • Journal Title: J Exp Med. 206(5) Pages: 1037-1046
• [Journal Article] A case of early-onset sarcoidosis with a six-base deletion in the NOD2 gene (2009)
  • Author(s): Sakai H, Ito S, Nishikomori R, Takaoka Y, Kawai T, Saito M, Okafuji I, Yasumi T, Heike T, Nakahata T.
  • Journal Title: Rheumatology (Oxford) 49 Pages: 194-196
  • Peer Reviewed
• [Journal Article] Orderly hematopoietic development of induced pluripotent stem cells via Flk-1(+) hemoangiogenic progenitors (2009)
  • Author(s): Niwa A, Umeda K, Chang H, Saito M, Okita K, Takahashi K, Nakagawa M, Yamanaka S, Nakahata T, Heike T.
  • Journal Title: J Cell Physiol. 221 Pages: 367-377
  • Peer Reviewed
• [Journal Article] Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria (2009)
  • Author(s): Nakamura Y, Kambe N, Saito M, Nishikomori R, Kim YG, Murakami M, Nunez G, Matsue H.
  • Journal Title: J Exp Med. 206 Pages: 1037-1046
  • Peer Reviewed
• [Journal Article] Role of the NOD2 genotype in the clinical phenotype of Blau syndrome and early-onset sarcoidosis (2009)
  • Author(s): Okafuji I, Nishikomori R, Kanazawa N, Kambe N, Fujisawa A, Yamazaki S, Saito M, Yoshioka T, Kawai T, Sakai H, Tanizaki H, Heike T, Miyachi Y, Nakahata T.
  • Journal Title: Arthritis Rheum. 60 Pages: 242-250
  • Peer Reviewed
• [Presentation] 疾患iPS細胞を用いたCINCA症候群の病態再現 (2011)
  • Author(s): 田中孝之、斎藤潤、中畑龍俊
  • Organizer: 免疫不全研究会
  • Place of Presentation: 福岡
  • Year and Date: 2011-01-22
• [Presentation] 疾患iPS細胞を用いた血液免疫疾患の疾患モデリングと病態解析 (2011)
  • Author(s): 齋藤潤
  • Organizer: 再生医療学会
  • Place of Presentation: 東京
• [Presentation] 疾患iPS細胞を用いた (2011)
  • Author(s): 田中孝之、斎藤潤、中畑龍俊
  • Organizer: CINCA症候群の病態再現免疫不全研究会
  • Place of Presentation: 福岡
• [Presentation] 免疫・血液疾患におけるES細胞・iPS細胞を用いた医療応用について (2010)
  • Author(s): 齋藤潤
  • Organizer: 兵庫小児血液懇話会
  • Place of Presentation: 神戸(招待講演)
  • Year and Date: 2010-11-20
• [Presentation] 疾患関連iPS細胞の応用:Bedside to bench and back (2010)
  • Author(s): 齋藤潤
  • Organizer: 第26回(2010)京都賞記念ワークショップ
  • Place of Presentation: 京都
  • Year and Date: 2010-11-12
• [Presentation] iPS細胞を用いた疾患研究の可能性について (2010)
  • Author(s): 齋藤潤
  • Organizer: 第129回臨床小児研究会
  • Place of Presentation: 埼玉(招待講演)
  • Year and Date: 2010-05-24
• [Presentation] 疾患関連iPS細胞の応用:Bedside to bench and back (2010)
  • Author(s): 齋藤潤
  • Organizer: 第26回京都賞記念ワークショップ先端技術部門シンポジウム
  • Place of Presentation: 京都(講演)
• [Presentation] 免疫・血液疾患におけるES細胞・iPS細胞を用いた医療応用について (2010)
  • Author(s): 斎藤潤
  • Organizer: 兵庫小児血液懇話会
  • Place of Presentation: 神戸(特別講演)
• [Presentation] iPS細胞を用いた疾患研究の可能性について (2010)
  • Author(s): 斎藤潤
  • Organizer: 第129回臨床小児研究会
  • Place of Presentation: 埼玉(特別講演)
• [Presentation] 原発性免疫不全症候群・Fanconi貧血・骨髄異形成症候群の解析 (2009)
  • Author(s): 齋藤潤
  • Organizer: 日本血液学会総会
  • Place of Presentation: 京都
• [Presentation] 再生医療の未来 (2009)
  • Author(s): 斎藤潤
  • Organizer: 第14回静岡健康・長寿学術フォーラム
  • Place of Presentation: 静岡(招待講演)
• [Book] 自己炎症性疾患の臨床所見と遺伝子異常を基礎とした治療は?(「EBM小児疾患の治療」) (2011)
  • Author(s): 齋藤潤、西小森隆太
  • Publisher: 中外医学社 東京
• [Book] 「EBM小児疾患の治療」pp374-380 (2011)
  • Author(s): 西小森隆太、斎藤潤
  • Total Pages: 771
  • Publisher: 中外医学社
• [Remarks] ホームページ等
• [Remarks]
  • URL: http://www.med.kyoto-u.ac.jp/J/gradschool/introduction/1118/
• [Patent(Industrial Property Rights)] インフラマソームの活性を抑える薬剤をスクリーニングする方法 (2010)
  • Inventor(s): 中畑龍俊/斎藤潤/田中孝之/山中伸弥
  • Industrial Property Rights Holder: 京都大学
  • Filing Date: 2010-11-18
  • Overseas
• [Patent(Industrial Property Rights)] インフラマソームの活性を抑える薬剤をスクリーニングする方法 (2010)
  • Inventor(s): 中畑龍俊/斎藤潤/田中孝之/山中伸弥
  • Industrial Property Rights Holder: 京都大学
  • Filing Date: 2010-11-18
  • Overseas