The role of visceral adipose tissue CD8+ T cells in obese murine asthma model

• Project/Area Number: 23591120
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Kochi University
• Principal Investigator: OHNISHI Hiroshi 高知大学, 教育研究部医療学系, 助教 (90553876)
• Research Collaborator: KOMIYAMA Shuzo 高知大学, 医学部, 技術補佐員
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 喘息 / CD8陽性T細胞 / 肥満 / 好酸球性気道炎症 / 気道過敏性 / CD8

Outline of Final Research Achievements

Obesity is associated with poorer control of asthma. CD8+ T cells contribute to adipose tissue inflammation. Effector CD8+ T cells are associated with asthma pathogenesis. We investigated whether visceral adipose tissue CD8+ T cells can enhance asthma phenotype in murine asthma model. Obese murine asthma model showed enhanced asthma phenotype compared with non-obese asthma model. Antigen inhalational challenge after adoptive transfer of mononuclear cells from visceral adipose tissue of allergen-sensitized obese mice failed to develop or enhance asthma phenotype in non-sensitized or secondary allergen-challenged non-obese mice. Adoptive transfer of visceral adipose tissue CD8+ T cells from obese mice suppressed asthma phenotype in allergen-sensitized and -challenged non-obese mice. These data suggested that visceral adipose tissue CD8+ T cells from obese mice might suppress the development of asthma phenotype.

Research Products

• [Journal Article] Seasonal variation of serum KL-6 concentrations is greater in patients with hypersensitivity pneumonitis. (2014)
  • Author(s): Ohnishi H, Miyamoto S, Kawase S, Kubota T, Yokoyama A.
  • Journal Title: BMC Pulm Med Volume: 14 Issue: 1 Pages: 129-129
  • DOI: 10.1186/1471-2466-14-129
  • Peer Reviewed / Open Access
• [Journal Article] GLCCI1 variant accelerates pulmonary function decline in patients with asthma receiving inhaled corticosteroids. (2014)
  • Author(s): Izuhara Y, Matsumoto H, Kanemitsu Y, Izuhara K, Tohda Y, Horiguchi T, Kita H, Kuwabara K, Tomii K, Otsuka K, Fujimura M, Ohkura N, Tomita K, Yokoyama A, Ohnishi H, Nakano Y, Oguma T, Hozawa S, Nagasaki T, Ito I, Oguma T, Inoue H, Tajiri T, Iwata T, Ono J, Ohta S, Tamari M, Hirota T, Yokoyama T, Niimi A, Mishima M.
  • Journal Title: Allergy Volume: 69 Issue: 5 Pages: 668-73
  • DOI: 10.1111/all.12400
  • Peer Reviewed / Open Access
• [Journal Article] Integrating longitudinal information on pulmonary function and inflammation using asthma phenotypes. (2014)
  • Author(s): Nagasaki T, Matsumoto H, Kanemitsu Y, Izuhara K, Tohda Y, Kita H, Horiguchi T, Kuwabara K, Tomii K, Otsuka K, Fujimura M, Ohkura N, Tomita K, Yokoyama A, Ohnishi H, Nakano Y, Oguma T, Hozawa S, Ito I, Oguma T, Inoue H, Tajiri T, Iwata T, Izuhara Y, Ono J, Ohta S, Yokoyama T, Niimi A, Mishima M
  • Journal Title: J Allergy Clin Immunol Volume: 133 Issue: 5 Pages: 1474-1477
  • DOI: 10.1016/j.jaci.2013.12.1084
  • Peer Reviewed / Open Access
• [Journal Article] Leukotriene B4 receptor 1 is differentially expressed on peripheral T cells of steroid-sensitive and -resistant asthmatics. (2014)
  • Author(s): Chung EH, Jia Y, Ohnishi H, 他6名
  • Journal Title: Ann Allergy Asthma Immunol. Volume: 112 Issue: 3 Pages: 211-216.e1
  • DOI: 10.1016/j.anai.2013.12.006
  • Peer Reviewed
• [Journal Article] IL-13-producing BLT1-positive CD8 cells are increased in asthma and are associated with airway obstruction. (2013)
  • Author(s): Dakhama A, Collins ML, Ohnishi H, 他６名
  • Journal Title: Allergy Volume: 68 Issue: 5 Pages: 666-73
  • DOI: 10.1111/all.12135
  • Peer Reviewed
• [Journal Article] Increased periostin associates with greater airflow limitation in patients receiving inhaled corticosteroids (2013)
  • Author(s): Kanemitsu Y, Mishima M,et al.
  • Journal Title: J Allergy Clin Immunol Volume: 132 Issue: 2 Pages: 305-312
  • DOI: 10.1016/j.jaci.2013.04.050
  • NAID: 120005342661
  • Peer Reviewed
• [Journal Article] A novel lung injury animal model using KL-6-measurable human MUC1- expressing mice (2013)
  • Author(s): Sakai M, Kubota T, Ohnishi H, Yokoya ma A
  • Journal Title: Biochem Biophys Res Commun Volume: 432 Issue: 3 Pages: 460-5
  • DOI: 10.1016/j.bbrc.2013.01.123
  • Peer Reviewed
• [Journal Article] Loss of T regulatory cell suppression following signaling through glucocorticoid-induced tumor necrosis receptor (GITR) is dependent on c-Jun N-terminal kinase activation. (2012)
  • Author(s): Joetham A, Ohnishi H, 他6名
  • Journal Title: J Biol Chem Volume: 287 Issue: 21 Pages: 17100-8
  • DOI: 10.1074/jbc.m111.316943
  • Peer Reviewed
• [Journal Article] CD8 regulates T regulatory cell production of IL-6 and maintains their suppressive phenotype in allergic lung disease. (2011)
  • Author(s): Joetham A, Okamoto M, Takeda K, Schedel M, Ohnishi H, 他2名
  • Journal Title: J Immunol. Volume: 186 Issue: 1 Pages: 113-20
  • DOI: 10.4049/jimmunol.1001663
  • Peer Reviewed
• [Journal Article] Chronic Hepatitis C Virus Infection is Associated with More Severe Asthma (2011)
  • Author(s): Nakashima T, Yokoyama A, Ohnishi H, 他7名
  • Journal Title: Allergology International Volume: 60 Issue: 3 Pages: 299-304
  • DOI: 10.2332/allergolint.10-OA-0240
  • NAID: 130004723041
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] Targeting CXCR3 reduces ligand-induced T-cell activation but not development of lung allergic responses. (2011)
  • Author(s): Shin YS, Takeda K, Ohnishi H, 他9名
  • Journal Title: Ann Allergy Asthma Immunol. Volume: 107 Issue: 2 Pages: 145-53
  • DOI: 10.1016/j.anai.2011.04.013
  • Peer Reviewed
• [Presentation] Activation of Extracellular Signal-Regulated Kinases 1/2 is Essential for the Development of CD8+ T cell-Mediated Allergic Airway Inflammation. (2012)
  • Author(s): Hiroshi Ohnishi
  • Organizer: East Asia Allergy Symposium
  • Place of Presentation: Grand Hilton Seoul (Seoul, Korea)
  • Invited
• [Presentation] Synergistic Effects of CD4+ and CD8+ T Cells for the Full Development of Allergen-Induced Airway Hyperresponsiveness Requires Leukotriene B4 Receptor-1 Expression. (2011)
  • Author(s): Ohnishi H, 他5名
  • Organizer: 2011 American Thoracic Society International conference
  • Place of Presentation: Denver, CO, USA（Colorado Convention Center）
• [Presentation] The role of leukotriene B4-dependent migration of T cells in allergic airway inflammation and airway hyperresponsiveness. (2011)
  • Author(s): Ohnishi H.
  • Organizer: 第61回日本アレルギー学会秋期学術大会 日韓中合同シンポジウム
  • Place of Presentation: 東京(グランドプリンスホテル新高輪）
• [Presentation] Full Development of Allergen-Induced Airway Hyperresponsiveness Requires Leukotriene B4 Receptor-1 Expression on Both CD4+ and CD8+ T Cells. (2011)
  • Author(s): Ohnishi H, 他4名
  • Organizer: 第51回日本呼吸器学会学術講演会
  • Place of Presentation: 東京(東京国際フォーラム）