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

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11202
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Kansai 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
• Keywords: Treg / 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

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.

Free Research Field

内耳免疫、難聴治療、

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。