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Prevention of age-related hearing loss by alteration of cellular immunity

Research Project

Project/Area Number 16K11202
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Otorhinolaryngology
Research InstitutionKansai Medical University

Principal Investigator

IWAI Hiroshi  関西医科大学, 医学部, 教授 (10232638)

Co-Investigator(Kenkyū-buntansha) 稲葉 宗夫  関西医科大学, 医学部, 非常勤講師 (70115947)
Research Collaborator INABA muneo  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
KeywordsTreg / IL-1 / 細胞性免疫 / 老人性難聴 / 酸化ストレス / 聴性脳幹反応 / 螺旋神経節 / 老化予防 / SAMP1 / IL-1R2 / 老化 / 胸腺萎縮 / 胸腺移植 / CD4 / IL-1タイプ2受容体
Outline of Final Research Achievements

Although age-related hearing loss (AHL) is an infamous disability deteriorating quality of life, we have not established its preventive measure. To overcome this situation, we focused cellular immunity related to development of AHL, especially three CD4+T cell fractions of interleukin 1 receptor type II-positive T cells (T1R2), naturally occurring regulatory T cells (Treg), and non-T1R2 and non-Treg (nTnI) which consists of CD4+T cells deleting both T1R2 and Treg.
Using SAMP1 murine inbred strain, a well-established model of aging with AHL, it was found that inoculation of nTnI fraction prevented not only the development of AHL, but also manifestation of degeneration in spiral ganglion (SG) neurons. Although no infiltration of lymphocytes was detected in SG, it is noted that nTnI successfully suppressed the nitric oxide (NO) level as oxidant stress in serum, indicating the relevance of oxidant stress to play a role in interaction between the systemic immune system and cochlea.

Academic Significance and Societal Importance of the Research Achievements

ヒトの抗加齢研究は長い観察期間を要し速やかな成果を得にくいため、今回、老化促進・早期難聴モデルマウスであるSAMP1を用いて実験を行った。このマウスはヒトと同じく加齢性の胸腺萎縮・細胞性免疫能低下・難聴(蝸牛の機能低下と萎縮)を示すため、全身免疫機構と聴覚とを検討する格好のモデルである。
今回の研究結果から、nTnI(老化・難聴に関与するTreg・T1R2が除去されたCD4+T細胞分画)の定期的な接種(全身細胞性免疫機能の若返り)にて、難聴を予防できることが明らかとなった。したがって、臨床においても同様の処置にて、老人性難聴、さらには広く老化予防(抗加齢療法)に発展できる可能性を考える。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (23 results)

All 2019 2018 2017 2016 Other

All Journal Article (19 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 19 results,  Open Access: 17 results) Presentation (3 results) (of which Int'l Joint Research: 1 results) Remarks (1 results)

  • [Journal Article] Cytological features of basal cell adenocarcinoma of the salivary glands.2019

    • Author(s)
      Ishida M, Okano K, Sandoh K, Ebisu Y, Fujisawa T, Iwai H, Tsuta K
    • Journal Title

      Diagn Cytopathol.

      Volume: - Issue: 7 Pages: 733-737

    • DOI

      10.1002/dc.24178

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Critical role of CCL4 in eosinophil recruitment into the airway2019

    • Author(s)
      Kobayashi Yoshiki、Konno Yasunori、Kanda Akira、Yamada Yoshiyuki、Yasuba Hirotaka、Sakata Yoshiko、Fukuchi Mineyo、Tomoda Koichi、Iwai Hiroshi、Ueki Shigeharu
    • Journal Title

      Clinical & Experimental Allergy

      Volume: - Issue: 6 Pages: 853-860

    • DOI

      10.1111/cea.13382

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantitative immunohistochemical assay with novel digital immunostaining for comparisons of PD-L1 antibodies.2019

    • Author(s)
      Fujisawa T, Tsuta K, Yanagimoto H, Yagi M, Suzuki K, Nishikawa K, Takahashi M, Okada H, Nakano Y, Iwai H
    • Journal Title

      Mol Clin Oncol

      Volume: -

    • DOI

      10.3892/mco.2019.1801

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical significance of periosteal reaction as a predictive factor for treatment outcome of medication-related osteonecrosis of the jaw.2019

    • Author(s)
      Kojima Y, Kawaoka Y, Sawada S, Hayashida S, Okuyama K, Yutori H, Kawakita A, Ishida S, Soutome S, Yanamoto S, Umeda M, Iwai H
    • Journal Title

      J Bone Miner Metab

      Volume: -

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cytological features of basal cell adenoma of salivary glands: Analysis of 19 cases emphasizing stromal spindle cells.2019

    • Author(s)
      Ishida M, Okano K, Sandoh K, Ebisu Y, Fujisawa T, Iwai H, Tsuta K
    • Journal Title

      Diagn Cytopathol

      Volume: - Issue: 7 Pages: 665-669

    • DOI

      10.1002/dc.24164

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Eosinophilic Upper Airway Inflammation in a Murine Model Using an Adoptive Transfer System Induces Hyposmia and Epithelial Layer Injury with Convex Lesions.2019

    • Author(s)
      Kanda A, Fujieda S, et al.
    • Journal Title

      Med Sci (Basel).

      Volume: 7(2) Issue: 2 Pages: 22-22

    • DOI

      10.3390/medsci7020022

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Collagenous crystalloids in pleomorphic adenoma of the parotid gland.2019

    • Author(s)
      Okano K, Arimoto T, Ishida M, Sandoh K, Fujisawa T, Iwai H, Tsuta K.
    • Journal Title

      Diagn Cytopathol.

      Volume: - Issue: 6 Pages: 612-613

    • DOI

      10.1002/dc.24149

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of Interaction between the Upper and Lower Airways in United Airway Disease.2019

    • Author(s)
      Kanda A, Kobayashi Y, Asako M, Tomoda K, Kawauchi H, Iwai H
    • Journal Title

      Med Sci (Basel)

      Volume: - Issue: 2 Pages: 27-27

    • DOI

      10.3390/medsci7020027

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metastatic salivary duct carcinoma in cardiac and pleural effusions: A case report with immunocytochemical analysis for androgen receptor and HER2.2019

    • Author(s)
      Ito H, Ishida M, Sando K, Okano K, Ebisu Y, Fujisawa T, Iwai H, Tsuta K
    • Journal Title

      Mol Clin Oncol

      Volume: -

    • DOI

      10.3892/mco.2018.1747

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 全身免疫機能改変による進行性蝸牛障害の予防と治療ーマウスモデルによる検討2018

    • Author(s)
      岩井 大
    • Journal Title

      耳鼻咽喉科展望

      Volume: 61 Pages: 12-23

    • NAID

      130007594839

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HFA-BDP Metered-Dose Inhaler Exhaled Through the Nose Improves Eosinophilic Chronic Rhinosinusitis With Bronchial Asthma: A Blinded, Placebo-Controlled Study2018

    • Author(s)
      Kobayashi Yoshiki、Yasuba Hirotaka、Asako Mikiya、Yamamoto Takahisa、Takano Hiroshi、Tomoda Koichi、Kanda Akira、Iwai Hiroshi
    • Journal Title

      Frontiers in Immunology

      Volume: 9 Pages: 2192-2192

    • DOI

      10.3389/fimmu.2018.02192

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A comparison of short-term outcomes of neck dissection for head and neck cancers using Thunderbeat, LigaSure or treatment without an energy-based device: A case controlled study.2018

    • Author(s)
      Suzuki K, Shimizu M, Sakagami T, Yagi M, Fujisawa T, Sawada S, Kanda A, Kobayashi Y, Iwai H
    • Journal Title

      Int J Surg

      Volume: - Pages: 60-64

    • DOI

      10.1016/j.ijsu.2018.09.009

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Indications for partial parotidectomy using retrograde dissection of the marginal mandibular branch of the facial nerve for benign tumours of the parotid gland.2018

    • Author(s)
      Suzuki K, Iwai H, Yagi M, Fujisawa T, Kanda A, Konishi M, Kobayashi Y, Tomoda K, Yamashita T.
    • Journal Title

      Br J Oral Maxillofac Surg

      Volume: - Issue: 8 Pages: 727-731

    • DOI

      10.1016/j.bjoms.2018.08.002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cells Expressing prominin-1 in neonatal murine inferior colliculus differentiate into neurons and glia.2018

    • Author(s)
      Okazaki H, Kanda A, Kanda S, Shimono T, Yun Y, Kobayashi Y, Wang Z, Ooka H, Suzuki K, Van DB, Tomoda K, Iwai H, Nishiyama T.
    • Journal Title

      Molecular Neurobiology

      Volume: 印刷中 Issue: 6 Pages: 4998-5005

    • DOI

      10.1007/s12035-017-0701-5

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 全身免疫機能改変による進行性蝸牛障害の予防と治療2018

    • Author(s)
      岩井 大
    • Journal Title

      耳展

      Volume: 61 Pages: 12-23

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Relationship between dental status and development of osteoradionecrosis of the jaw: a multicenter retrospective study.2017

    • Author(s)
      Kojima Y, Yanamoto S, Umeda M, Kawashita Y, Saito I, Hasegawa T, Komori T, Ueda N, Kirita T, Yamada SI, Kurita H, Senga Y, Shibuya Y, Iwai H.
    • Journal Title

      Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

      Volume: 124 Issue: 2 Pages: 139-145

    • DOI

      10.1016/j.oooo.2017.04.012

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hematogenous renal cell carcinoma metastasis in the postoperative temporal bone.2017

    • Author(s)
      Konishi M, Suzuki K, Iwai H
    • Journal Title

      Case Reports in Oncology

      Volume: 24 Issue: 1 Pages: 212-216

    • DOI

      10.1159/000460243

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mammary analogue secretory carcinoma presenting as a cervical lymph node metastasis of unknown primary site: a case report.2017

    • Author(s)
      Suzuki K, Yagi M, Kanda A, Kobayashi Y, Konishi M, Miyasaka C, Tashiro T, Iwai H.
    • Journal Title

      Case Reports in Oncology

      Volume: 15 Issue: 1 Pages: 192-198

    • DOI

      10.1159/000457949

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reexamination of etiology and surgical outcome in patient with advanced external auditory canal cholesteatoma.2016

    • Author(s)
      Konishi M, Iwai H, Tomoda K
    • Journal Title

      Otology and Neurotology

      Volume: 37 Issue: 6 Pages: 728734-728734

    • DOI

      10.1097/mao.0000000000001079

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Prevention of age-related hearing loss by transfer of CD4-positive T cells deleting IL-1 receptor type 2-positive T cells and regulatory T cells2018

    • Author(s)
      Iwai H, Inaba M, Van DB, Yun Y, Kobayashi Y, Kanda A, Fujisawa T, Yagi M
    • Organizer
      55th Inner Ear Biology Workshop 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 老人性難聴モデルマウスにおける CD4+リンパ球分画移入による難聴予防2018

    • Author(s)
      岩井 大,Van DB,鈴木健介,小林良樹,尹 泰貴,高田洋平,福井英人,神田 晃, 稲葉宗夫
    • Organizer
      日本耳鼻咽喉科免疫アレルギー学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 老人性難聴モデルマウスにおけるCD4+Tリンパ球分画移入による難聴予防2018

    • Author(s)
      岩井 大、Van DB、鈴木健介、小林良樹、尹 泰貴、高田洋平、福井英人、神田 晃、稲葉宗夫
    • Organizer
      耳鼻咽喉科ニューロサイエンス研究会
    • Related Report
      2018 Annual Research Report
  • [Remarks] 関西医科大学耳鼻咽喉科・頭頸部外科学教室 研究のご紹介 研究紹介04

    • URL

      http://www7.kmu.ac.jp/ent/research/04.html

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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