Abstract
BackgroundAccumulating evidence has indicated the relationship between the systemic immune system and the central nervous system including the inner ear.ResultsWe have shown that age-related developments of T-cell dysfunction, hearing loss, and degeneration of cochlear spiral ganglion (SG) neurons observed in 6-month-old mice were recovered in 12 months old mice which previously given fetal thymus transplants twice. We have also demonstrated 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.ConclusionIt 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 cells accelerate both age-related hearing loss (AHL) and neurodegeneration of the cochlear neurons. Further studies on the interactions among IL-1R2 expression on CD4+ T cells, Tregs, and neuronal cells and also on the relationships between fetal thymus grafting and the rejuvenation of systemic immunity should be designed in order to advance towards therapeutic effects on neurosenescence, including AHL.
Highlights
Accumulating evidence has indicated the relationship between the systemic immune system and the central nervous system including the inner ear
We have found that up-regulation of the expression of interleukin 1 receptor type 2 (IL-1R2) genes in CD4+ T cells is associated with age-related developments of hearing loss, spiral ganglion (SG) degeneration, and the dysfunction of cellular immunity, and that the rejuvenation of recipient immunity by the inoculation of young CD4+ T cells or a fetal thymus graft leads to down-regulation of the genes in CD4+ T cells and reduces these features of senescence [21]
We previously demonstrated that these mice do not show Age-related hearing loss (AHL) upon the inoculations of CD4+ T cells from a syngeneic donor aged 2 months old twice at a two-month interval or can avoid AHL and SG neuron loss by syngeneic fetal thymus grafting at 2 months old [21]
Summary
Accumulating evidence has indicated the relationship between the systemic immune system and the central nervous system including the inner ear. Age-related hearing loss (AHL), known as presbycusis, is a universal feature of mammalian aging and involves genetic, cellular, and systemic-level changes in the auditory part of the inner ear, namely, the cochlea, and the part of the brain used for hearing, namely, the central auditory pathway [3]. Recent research in gerontology has shown that inflammaging, a state of chronic systematic inflammation associated with age, is a consequence of immunosenescence, the aging of the immune system, and contributes to the aging process and the development of age-related disabilities and diseases including AHL [4]. Local inner ear immunity is part of the overall systemic response and can induce cochlear degeneration and hearing loss [3, 7,8,9]
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