Basic Research for a Clarification of Mechanisms and a Clinical Use to Regulate Th2 Condition by Treg Subset

• Project/Area Number: 19790704
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: National Research Institute for Child Health and Development
• Principal Investigator: ORIHARA Kanami National Research Institute for Child Health and Development, 免疫アレルギー研究部, 共同研究員 (60450623)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥2,400,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥1,100,000 (Direct Cost: ¥1,100,000)
• Keywords: 制御性T細胞 / Th2 / アレルギー / Foxp3 / Tr1 / IL-10

Research Abstract

本研究では、複数のTreg subtypeを含むT細胞群を同一の系で扱うことにより、これらの分類の境界線を明確にするとともに、それぞれの制御能を検証していることに特徴としていた。それらのTregを活性化、活性化T細胞と共培養した上清中のサイトカインバランスを他種類コントロール細胞上清と比較検討することにより、そのTh1/Th2制御能を検証したことにより、それぞれの特徴が見えてきた。制御に関してのみならず、それぞれが異なる分化経路をたどっており、その鍵となる分子の候補も絞られてきた。
Foxp3+CD4+細胞がアレルギー疾患の診断に応用できることを明らかにし、治療、予防方法の一つとしてTr1の応用が候補になることも示してきた。これらにより、日本の小学生の約半数にまで増加してしまったアレルギー発症率の低下、重症度の軽減に一歩でも近づく医療体制実現への可能性が期待される。

Research Products

• [Journal Article] TH2 cytokines potently induce an appetite-stimulating peptide, melanin-concentrating hormone, in human vascular endothelial cells (2009)
  • Author(s): Orihara K, et al
  • Journal Title: J Allergy Clin Immunol 未定
  • Peer Reviewed
• [Journal Article] Tissue remodeling by hypersecreted EGF and amphiregulin in the airway following an acute asthma attack (2009)
  • Author(s): Enomoto Y, Orihara K, et al
  • Journal Title: J Allergy Clin Immunol 未定
  • Peer Reviewed
• [Journal Article] IL-33 mediates inflammatory responses in human pulmonary microvascular endothelial cells and epithelial cells (2009)
  • Author(s): Orihara K, Yagami, A, et al
  • Journal Title: J Allergy Clin Immunol 未定
  • Peer Reviewed
• [Journal Article] Tissue remodeling by hypersecreted EGF and amphiregulin in the airway following an acute asthma attack (2009)
  • Author(s): Enomoto Y, Orihara K, et al.
  • Journal Title: J Allergy Clin Immunol (未定)
  • Peer Reviewed
• [Journal Article] Role of regulatory and proinflammatory T cell populations in allergic diseases (2008)
  • Author(s): Orihara K, et. Al
  • Journal Title: WAO Journal 1 Pages: 9-14
  • Peer Reviewed
• [Journal Article] Corticosteroid enhances TNF-α-mediated leukocyte adhesion to pulmonary microvascular endothelial cells (2008)
  • Author(s): Matsuda A, Orihara K, et. Al
  • Journal Title: Allergy 63 Pages: 1610-6
  • Peer Reviewed
• [Journal Article] Pathophysiolosical roles of microvascular alterations in pulmonary inflammatory diseases: Possible implications of tumor necrosis factor-alpha and CXC chmokines (2008)
  • Author(s): Orihara K, Matsuda A
  • Journal Title: Int J Chron Obstruct Pulmon Dis 3-4 Pages: 619-27
  • Peer Reviewed
• [Journal Article] Pathophysiolosical roles of microvascular alterations in pulmonary inflamminatory diseases: Possible implications of tumor necrosis factor-alpha and CXC chmokines (2008)
  • Author(s): Orihara K, Matsuda A.
  • Journal Title: Int J Chron Obstruct Pulmon Dis. 3-4 Pages: 619-27
  • Peer Reviewed
• [Journal Article] Role of regulatory and proinflammatory T cell populations in allergic diseries (2008)
  • Author(s): Orihara K, et. al.
  • Journal Title: WAO Journal 1 Pages: 9-14
  • Peer Reviewed
• [Journal Article] Corticosteroid enhances TNF-α-mediated leukocyte adhesion to puhnonary microvascular endothelial cells (2008)
  • Author(s): Matsuda A, Orihara K, et. al.
  • Journal Title: Allergy (未定)
  • Peer Reviewed
• [Journal Article] Circulating Foxp3+CD4+ cell number in atopic patients and healthy controls (2007)
  • Author(s): Orihara K, et. Al.
  • Journal Title: J Allergy Clin Immunol 120 Pages: 960-962
  • Peer Reviewed
• [Journal Article] Circulating Foxp^3+CD4+cell number in atopic patients and healthy controls (2007)
  • Author(s): Orihara K, et. al.
  • Journal Title: J Allergy Clin Immunol 120 Pages: 960-962
  • Peer Reviewed
• [Journal Article] TH2 cytokines potently induce an appetite-stimulating peptide, melanin-concentrating hormone, in human vascular endothelial cells
  • Author(s): Orihara K, et al.
  • Journal Title: J Allergy Clin Immunol (未定)
  • Peer Reviewed
• [Journal Article] IL-33 mediates inflammatory responses in human pulmonary microvascular endothelial cells and epithelial cells
  • Author(s): Orihara K, Yagami ,A, et al.
  • Journal Title: J Allergy Clin Immunol (未定)
  • Peer Reviewed
• [Presentation] IL-33 mediates inflammatory responses in human airway epithelial cells and microvascular endothelial cells (2009)
  • Author(s): Orihara K
  • Organizer: 65th Annual Meeting of American Academy of Allergy, Asthma and Immunology
  • Place of Presentation: Washington, D.C.
• [Presentation] IL-33 mediates inflammatory responses in human airway epithelial cells and microvascular endothelial cells (2009)
  • Author(s): Orihara K
  • Organizer: 65th Annual Meeting of American Academy of Alergy, Asthma and Immunology
  • Place of Presentation: Washington, D.C.
• [Presentation] In Vitro Adverse Effects of Corticosteroid on TNF-α-mediated Responses by Pulmonary Microvascular Endothelial Cells (2008)
  • Author(s): Orihara K, et. Al
  • Organizer: 64th Annual Meeting of American Academy of Allergy, Asthma and Immunology
  • Place of Presentation: Philadelphia, PA, USA
• [Presentation] In vitro corticosteroid treatment enhances TNF-α-mediated inflammatory reactions of pulmonary microvascular endothelial cells (2008)
  • Author(s): Orihara K
  • Organizer: Collegium Internationale Allergologicum 27th Symposium
  • Place of Presentation: Curacao
• [Presentation] In vitro corticosteroid treatment enhances TNF-α-mediated inflammatory reactions of pulmonary microvascular endothelial cells (2008)
  • Author(s): Orihara K
  • Organizer: Collegium Internationale Allergologicum 27th posium
  • Place of Presentation: Curacao
• [Presentation] In Vitro Adverse Effects of Corticosteroid on TNF-α-mediated Responses by Pulmonary Microvascular Endothelial Cells. (2008)
  • Author(s): OriharaK, et. al.
  • Organizer: 64th Annual Meeting of American AcademyofAll ergy, Asthma and lmmunology
  • Place of Presentation: Philadelphia,PA,USA
• [Presentation] Differences in Foxp3+CD4+ ratio between symptomatic atopic patients and asymptomatic atopic controls with similar levels of Th1/Th2 markers (2007)
  • Author(s): Orihara K, et. Al
  • Organizer: 20th World Allergy Congress
  • Place of Presentation: Bangkok, Thailand
• [Presentation] Differences in Foxp3^+CD4^+ratio between symptomatic atopic patients and asymptomatic atopic controls with similar levels of Thl/Th2 markers. (2007)
  • Author(s): OriharaK, et. al.
  • Organizer: 20th WorldAllergyCongress
  • Place of Presentation: Bangkok,Thailad
• [Remarks] ホームページ等
  • URL: http://www.nch.go.jp/imal/default.htm
• [Remarks]
  • URL: http://www.nch.go.jp/imal/default.htm
• [Patent(Industrial Property Rights)] アレルギー疾患推定マーカー及び治療効果判定マーカー、並びに、それらの利用方法 (2007)
  • Inventor(s): 斎藤博久、松本健治
  • Industrial Property Rights Holder: 国立成育医療センター総長、ヒューマンサイエンス財団
  • Filing Date: 2007-07-05
• [Patent(Industrial Property Rights)] アレルギー疾患推定マーカー及び治療効果判定マーカー、並びに、それらの利用方法 (2007)
  • Inventor(s): 斎藤 博久、 松本 健治
  • Industrial Property Rights Holder: 国立成育医療センター総長、ヒューマンサイエンス財団
  • Filing Date: 2007-07-05