Thymus transplantation therapy for age-related hearing loss and analysis of the mechanism of thymus functions

• Project/Area Number: 25462655
• 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): INABA Muneo 関西医科大学, 医学部, 非常勤講師 (70115947)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 老人性難聴 / CD４陽性Tリンパ球 / Treg / IL-1受容体2型 / 螺旋神経節 / 聴性脳幹反応 / 胸腺移植 / 細胞性免疫 / 細胞免疫 / 螺旋神経節細胞 / CD4＋リンパ球 / nTreg / 早期老化 / SAMP1 / 蝸牛 / 胸腺萎縮

Outline of Final Research Achievements

Accumulating evidence has indicated the relationship between the systemic immune system and the central nervous system including the inner ear. We have found that age-related developments of T-cell dysfunction, hearing loss, and degeneration of cochlear spiral ganglion (SG) neurons in 6-month-old mice were recovered at 12 months old after fetal thymus transplants were given twice, and that CD4+ T cells expressing interleukin 1 receptor type 2 (IL-1R2) and naturally occurring regulatory T cells (nTregs), which expanded in aged 12-month-old mice, were reduced in the thymus-grafted mice of the same age. Therefore, it is conceivable that the rejuvenation of systemic immune function by fetal thymus grafts contributes not only to the activation of cellular immunity but also to the decrease of IL-1R2+ CD4+ T cells or nTregs, which cause age-related hearing loss (AHL) as a consequence of neurodegeneration of the cochlear neurons.

Research Products

• [Journal Article] Fetal thymus graft enables recovery from age-related hearing loss and expansion of CD4-psitive T cells expressing IL-1 receptor type 2 and regulatory T cells. (2015)
  • Author(s): Iwai H, Inaba M.
  • Journal Title: Immuniy & Ageing Volume: 12:26 Issue: 1 Pages: 1-10
  • DOI: 10.1186/s12979-015-0053-9
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Fetal thymus graft enables recovery from age-related hearing loss and expansion of CD4-positive T cells expressing IL-1 receptor Type 2 and regulatory T cells. (2015)
  • Author(s): Iwai H, Inaba M.
  • Organizer: 52nd Inner Ear Biology Workshop
  • Place of Presentation: Roma, Italy
  • Year and Date: 2015-09-12
  • Int'l Joint Research