Mechanisms of impaired function of CD4+CD25+FOXP3+ T cells in patients of asthma

• Project/Area Number: 24591471
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Showa University
• Principal Investigator: NEGORO TAKAHARU 昭和大学, 薬学部, 講師 (70218270)
• Co-Investigator(Kenkyū-buntansha): NAKANO Yasuko 昭和大学, 薬学部, 教授 (20155790)
• Project Period (FY): 2012-04-01 – 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 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 制御性T細胞 / カルシウム / RACK1 / 酸化ストレス / ペルオキシレドキシン / ERK / 国際情報交換 / イギリス：スペイン / アレルギー疾患 / カルシウムチャネル / カルシウムイオン / 免疫抑制 / CRACチャネル / イギリス：スペイン：アメリカ

Outline of Final Research Achievements

One of the asthma pathologies is a persistent inflammation in airway caused by allergens and viruses. The impaired functions and decreased number of regulatory T cells (Tregs) is considered as the cause of persistent inflammation in local sites. The mechanisms of abnormal functions of Tregs are obscure. Therefore, the aim of this study was to analyze the functions of Tregs by using Ca2+ response against T cell receptor stimulation, which can estimate the regulatory functions of Tregs, and to elucidate the mechanisms of abnormal functions of Tregs. The results showed that increasing Ca2+ response in Tregs from patients with asthma was attributed to the increasing expression of scaffold protein, RACK1. In addition, the new data associated with the abnormal functions of Tregs was obtained from microarray analysis.

Research Products

• [Journal Article] Elevated receptor for activated C kinase 1 expression is involved in intracellular Ca2+ influx and potentially associated with compromised regulatory T cell function in patients with asthma (2014)
  • Author(s): Negoro T, Shimizu S, Narushima M, Banham AH, Wakabayashi H, Takayanagi R, Hagiwara T, Roncador R, Osabe T, Yanai T, Kin T, Ikeda K, Endo A, Akiyama H, Nakano Y
  • Journal Title: Clin Exp Allergy Volume: 44 Issue: 9 Pages: 1154-1169
  • DOI: 10.1111/cea.12375
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Inhibitory effects of AG490 on H2O2-induced TRPM2-mediated Ca(2+) entry (2014)
  • Author(s): Shimizu S, Yonezawa R, Hagiwara T, Yoshida T, Takahashi N, Hamano S, Negoro T, Toda T, Wakamori M, Mori Y, Ishii M
  • Journal Title: Eur J Pharmacol Volume: 742 Pages: 22-30
  • DOI: 10.1016/j.ejphar.2014.08.023
  • Peer Reviewed
• [Journal Article] A simple smart amplification assay for the rapid detection of human cytomegalovirus in the urine of neonates (2014)
  • Author(s): Kohda C, Chiba N, Shimokoba K, Mizuno K, Negoro T, Nakano Y, Tanaka K
  • Journal Title: J Virol Methods Volume: 208 Pages: 160-165
  • DOI: 10.1016/j.jviromet.2014.07.034
  • Peer Reviewed / Open Access
• [Journal Article] Potentiated macrophage activation by acid sensing under low adiponectin levels. (2014)
  • Author(s): Negoro T, Kin M, Takuma A, Saito K, Shimizu S, Nakano Y
  • Journal Title: Mol Immunol Volume: 57 Issue: 2 Pages: 141-150
  • DOI: 10.1016/j.molimm.2013.08.015
  • Peer Reviewed
• [Journal Article] Metformin modulates GLP-1- and GIP-mediated intracellular signaling under normoglycemic conditions (2013)
  • Author(s): K Shinmura, T Negoro, S Shimizu, G Roncador, T Hirano, Y Nakano
  • Journal Title: Open J Endocr and Metab Dis Volume: 3 Issue: 07 Pages: 263-270
  • DOI: 10.4236/ojemd.2013.37036
  • Peer Reviewed
• [Journal Article] Neutrophil TRPM2 channels are implicated in the exacerbation of myocardial ischaemia/reperfusion injury (2013)
  • Author(s): Hiroi T, Wajima T, Negoro T, Ishii M, Yasuko Nakano, Kiuchi K, Mori Y, and Shimizu S
  • Journal Title: Cardiovasc Res Volume: vol.97 Issue: 2 Pages: 271-281
  • DOI: 10.1093/cvr/cvs332
  • Peer Reviewed
• [Journal Article] Adiponectin enhances calcium-dependency of mouse bladder contraction mediated by protein kinase Cα expression. (2013)
  • Author(s): Nobe K, Fujii A, Saito K, Negoro T, Ogawa Y, Nakano Y, Hashimoto T, Honda K.
  • Journal Title: J Pharmacol Exp Ther Volume: 345 Issue: 1 Pages: 62-68
  • DOI: 10.1124/jpet.112.202028
  • Peer Reviewed
• [Journal Article] Low HCMV DNA Copies Can Establish Infection and Result in Significant Symptoms in Extremely Preterm Infants: A Prospective Study. (2012)
  • Author(s): Wakabayashi H, Mizuno K, Kohda C, Negoro T, Maekawa C, Sawato S, Tanaka K, Nakano Y, Murayama J, Taki M, Miyazawa T, Murase M, Aizawa M, Nakano Y, Sakurai M, Takahashi K, Itabashi K.
  • Journal Title: Am J Perinatol Volume: 29 Issue: 05 Pages: 377-382
  • DOI: 10.1055/s-0031-1300971
  • Peer Reviewed
• [Presentation] Potentiated macrophage activation by acid sensing under low adiponectin levels (2012)
  • Author(s): T Negoro, H Akiyama, T Tanioka, K Saito, S Shimiz
  • Organizer: The 64th Fujihara Seminar
  • Place of Presentation: 北海道苫小牧市
• [Presentation] 関節リウマチにおけるアディポネクチンの生理的機能解明 (2012)
  • Author(s): 秋山晴代，嶋田紘也，齊藤清美，根来孝治，中野泰子
  • Organizer: 第35回 日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場
• [Book] Bronchial asthma-Emerging therapeutic strategies Chapter 4; Immunomechanisms of childhood asthma (2012)
  • Author(s): T Negoro, Y Yamamoto, S Shimizu, AH Banham, G Roncador, H Wakabayashi, T Osabe, T Yanai, H Akiyama, K Itabashi and Y Nakano
  • Total Pages: 260
  • Publisher: InTech
• [Remarks] 昭和大学学術業績リポジトリ
  • URL: http://meta.lilitory.showa-u.ac.jp/
• [Remarks] 昭和大学薬学部薬物療法学講座遺伝解析薬学部門 2013業績
  • URL: http://www.showa-u.ac.jp/sch/pharm/major/medinfo/rsch_achievement/2013.html
• [Remarks] 昭和大学薬学部薬物療法学講座遺伝解析薬学部門 2012年業績
  • URL: http://www.showa-u.ac.jp/sch/pharm/major/medinfo/rsch_achievement/2012.html