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<p>The olfactory epithelium (OE) undergoes life-long renewal and regeneration. This process is supported by the globose basal cells (GBC) during the homeostatic state, as well as horizontal basal cells (HBC) during severe damage. Inflamm-aging refers to the low-grade, chronic and progressive state of heightened pro-inflammation associated with aging. However, the impact of inflamm-aging on OE homeostasis, regeneration, and the inflammatory microenvironment is not fully understood. In this study using mouse models, we elucidate the role of interleukin-17a (IL-17a) in OE regeneration and olfactory function. Our findings implicate that inflamm-aging in aged OE promotes the recruitment and activation of immune cells, accompanied by crosstalk between HBC and T cells. Elevated expression of IL-17a in aged OE triggers inflammatory signals and impairs olfactory function. Administration of IL-17a inhibitor Y-320 or neutralizing antibody promotes sensory neuronal regeneration and reverses age-related respiratory metaplasia in OE. Co-culturing mouse OE organoids with Th17 cells impairs neuronal generation and enhances the transformation towards respiratory cells, while neutralizing antibody against IL-17a alleviates neuronal loss and respiratory transformation. Additionally, conditional knockout of IL-17a in T cells facilitates OE regeneration by promoting HBC recruitment and differentiation into GBC. Collectively, our study identifies a function of IL-17a in OE regeneration and age-related deficits in olfactory function, providing evidence for further investigation of IL-17a as a possible therapeutic target against presbyosmia.</p>

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IL-17a induces age-related olfactory dysfunction by impairing regeneration and promoting respiratory metaplasia in mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月29日

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  • Shenglei Wang,
  • Xudong Cha,
  • Yingqi Xie,
  • Zengyi Xu,
  • Boyu Cai,
  • Fengzhen Li,
  • Tengfei Li,
  • Zhe Wang,
  • Tianyu Wang,
  • Yiqun Yu,
  • Huanhai Liu,
  • Wenwen Ren

摘要

The olfactory epithelium (OE) undergoes life-long renewal and regeneration. This process is supported by the globose basal cells (GBC) during the homeostatic state, as well as horizontal basal cells (HBC) during severe damage. Inflamm-aging refers to the low-grade, chronic and progressive state of heightened pro-inflammation associated with aging. However, the impact of inflamm-aging on OE homeostasis, regeneration, and the inflammatory microenvironment is not fully understood. In this study using mouse models, we elucidate the role of interleukin-17a (IL-17a) in OE regeneration and olfactory function. Our findings implicate that inflamm-aging in aged OE promotes the recruitment and activation of immune cells, accompanied by crosstalk between HBC and T cells. Elevated expression of IL-17a in aged OE triggers inflammatory signals and impairs olfactory function. Administration of IL-17a inhibitor Y-320 or neutralizing antibody promotes sensory neuronal regeneration and reverses age-related respiratory metaplasia in OE. Co-culturing mouse OE organoids with Th17 cells impairs neuronal generation and enhances the transformation towards respiratory cells, while neutralizing antibody against IL-17a alleviates neuronal loss and respiratory transformation. Additionally, conditional knockout of IL-17a in T cells facilitates OE regeneration by promoting HBC recruitment and differentiation into GBC. Collectively, our study identifies a function of IL-17a in OE regeneration and age-related deficits in olfactory function, providing evidence for further investigation of IL-17a as a possible therapeutic target against presbyosmia.