2. Academic Validation
  3. IL-17a induces age-related olfactory dysfunction by impairing regeneration and promoting respiratory metaplasia in mice

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

  • Nat Commun. 2025 Dec 29. doi: 10.1038/s41467-025-67786-2.
Shenglei Wang # 1,  Xudong Cha # 1,  Yingqi Xie # 1,  Zengyi Xu # 1,  Boyu Cai 1 2,  Fengzhen Li 1,  Tengfei Li 1,  Zhe Wang 1,  Tianyu Wang 1,  Yiqun Yu 3 4,  Huanhai Liu 5,  Wenwen Ren 6
Affiliations

Affiliations

  • 1 Department of Otolaryngology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, PR China.
  • 2 Department of ORL-HNS, Shanghai Fourth People's Hospital, and School of Medicine, Tongji University, Shanghai, PR China.
  • 3 Ear, Nose & Throat Institute, Department of Otolaryngology, Eye, Ear, Nose & Throat Hospital, Fudan University, Shanghai, PR China. [email protected].
  • 4 Olfactory Disorder Diagnosis and Treatment Center, Eye, Ear, Nose & Throat Hospital, Fudan University, Shanghai, PR China. [email protected].
  • 5 Department of Otolaryngology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, PR China. [email protected].
  • 6 Department of Otolaryngology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, PR China. [email protected].
  • # Contributed equally.
PMID: 41461651 DOI: 10.1038/s41467-025-67786-2
Abstract

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.

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