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image of The Role of Interleukin-4 in Olfactory Epithelial Cells: A Preliminary In Vitro Study

Abstract

Introduction

Olfactory epithelium (OE) comprises diverse cell types, including olfactory sensory neurons (OSNs), supporting cells, and basal stem cells. While interleukin (IL)-4 is a key mediator in type 2 inflammation, its regulatory role in OE remains unclear. The current study aimed to explore the role of IL-4 in olfactory epithelial cells.

Methods

Using an olfactory epithelial organoid model, the impacts of IL-4 on different cell types were assessed by performing qPCR, immunofluorescence staining, and EdU incorporation assays. Calcium imaging was performed to assess the influence of IL-4 on OSNs, while Alcian Blue-Periodic Acid-Schiff (AB-PAS) staining was used to analyze mucin secretion in the organoids.

Results

IL-4 significantly promoted the proliferation of globular basal cells (GBCs) in basal cells, induced homeostasis of mature OSNs, and maintained the normal function of OE. However, IL-4 notably downregulated GAP43 expression in immature OSNs. Additionally, IL-4 enhanced mucin secretion in the OE.

Discussion

This study found that IL-4 promoted the differentiation of OE cells by stimulating the proliferation of GBCs and enhancing mucin secretion, while maintaining the normal function of mature olfactory neurons. Further clinical studies are needed to validate these results.

Conclusion

This study revealed the role of IL-4 in OE, providing novel insights into the mechanisms of IL-4 in inflammatory conditions.

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2025-09-25
2025-11-01

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References

  1. Kikuta S. Nagayama S. Hasegawa-Ishii S. Structures and functions of the normal and injured human olfactory epithelium. Front. Neural Circuits 2024 18 1406218 10.3389/fncir.2024.1406218 38903957
    [Google Scholar]
  2. Louie J.D. Bromberg B.H. Zunitch M.J. Schwob J.E. Horizontal basal cells self-govern their neurogenic potential during injury-induced regeneration of the olfactory epithelium. Development 2023 150 12 dev201552 10.1242/dev.201552 37260223
    [Google Scholar]
  3. Gameiro J.G. Hintschich C.A. Dekeyser A. Quiescent horizontal basal stem cells act as a niche for olfactory neurogenesis in a mouse 3D organoid model. Cell Rep Methods 2025 5 6 101055 10.1016/j.crmeth.2025.101055 40441150
    [Google Scholar]
  4. Liberia T Martin-Lopez E Meller SJ Greer CA Sequential maturation of olfactory sensory neurons in the mature olfactory epithelium. eNeuro 2019 6 5 ENEURO.0266-19.2019 10.1523/ENEURO.0266‑19.2019 31554664
    [Google Scholar]
  5. Bryche B. Baly C. Meunier N. Modulation of olfactory signal detection in the olfactory epithelium: Focus on the internal and external environment, and the emerging role of the immune system. Cell Tissue Res. 2021 384 3 589 605 10.1007/s00441‑021‑03467‑y 33961125
    [Google Scholar]
  6. Li Z. Wei M. Shen W. Kulaga H. Chen M. Lane A.P. Sox2 regulates globose basal cell regeneration in the olfactory epithelium. Int. Forum Allergy Rhinol. 2022 12 3 286 292 10.1002/alr.22890 34569176
    [Google Scholar]
  7. Zedan A. Winters A.D. Yu W. Antiviral functions of type I and type III interferons in the olfactory epithelium. Biomolecules 2023 13 12 1762 10.3390/biom13121762 38136633
    [Google Scholar]
  8. Dekeyser A. Huart C. Hummel T. Hox V. Olfactory loss in rhinosinusitis: Mechanisms of loss and recovery. Int. J. Mol. Sci. 2024 25 8 4460 10.3390/ijms25084460 38674045
    [Google Scholar]
  9. Schleimer R.P. Immunopathogenesis of chronic rhinosinusitis and nasal polyposis. Annu. Rev. Pathol. 2017 12 1 331 357 10.1146/annurev‑pathol‑052016‑100401 27959637
    [Google Scholar]
  10. Bernstein Z.J. Shenoy A. Chen A. Heller N.M. Spangler J.B. Engineering the IL ‐4/IL ‐13 axis for targeted immune modulation. Immunol. Rev. 2023 320 1 29 57 10.1111/imr.13230 37283511
    [Google Scholar]
  11. Olaguibel J.M. Sastre J. Rodríguez J.M. del Pozo V. Eosinophilia induced by blocking the IL-4/IL-13 pathway: Potential mechanisms and clinical outcomes. J. Investig. Allergol. Clin. Immunol. 2022 32 3 165 180 10.18176/jiaci.0823 35522053
    [Google Scholar]
  12. Tsuda T. Fujii S. Obata S. Central compartment of nasal cavity-derived MMP-9 enhances mixed-type 2 inflammation in eosinophilic chronic rhinosinusitis. Int. Immunol. 2025 37 9 551 561 10.1093/intimm/dxaf025 40333919
    [Google Scholar]
  13. Gandhi N.A. Pirozzi G. Graham N.M.H. Commonality of the IL-4/IL-13 pathway in atopic diseases. Expert Rev. Clin. Immunol. 2017 13 5 425 437 10.1080/1744666X.2017.1298443 28277826
    [Google Scholar]
  14. Hara Y. Jha M.K. Huang J.Y. The IL ‐4– IL ‐ 4Rα axis modulates olfactory neuroimmune signaling to induce loss of smell. Allergy 2025 80 2 440 461 10.1111/all.16338 39418114
    [Google Scholar]
  15. Krempski J. Yamani A. Thota L.N.R. IL-4–STAT6 axis amplifies histamine-induced vascular endothelial dysfunction and hypovolemic shock. J. Allergy Clin. Immunol. 2024 154 3 719 734 10.1016/j.jaci.2024.05.009 38777155
    [Google Scholar]
  16. Cai X.T. Jia M. Heigl T. IL-4-induced SOX9 confers lineage plasticity to aged adult lung stem cells. Cell Rep. 2024 44 7 114569 10.1016/j.celrep.2024.114569 39088319
    [Google Scholar]
  17. Cergan R. Berghi O. Dumitru M. Interleukin 8 molecular interplay in allergic rhinitis and chronic rhinosinusitis with nasal polyps: A scoping review. Life 2025 15 3 469 10.3390/life15030469 40141813
    [Google Scholar]
  18. Gong Q. Culture of mouse olfactory sensory neurons. Curr Protoc Neurosci 2012 Unit3.24. 10.1002/0471142301.ns0324s58 23042501
    [Google Scholar]
  19. Jia Z. Wang J. Li X. Yang Q. Han J. Repair effect of siRNA double silencing of the novel mechanically sensitive ion channels Piezo1 and TRPV4 on an osteoarthritis rat model. Curr. Mol. Pharmacol. 2024 17 18761429317745 10.2174/0118761429317745241017114020 39660528
    [Google Scholar]
  20. Hu L. Cao H. Zheng L. Li R. BBOX1-AS1 activates hedgehog signaling pathway to facilitate the proliferation and stemness of esophageal squamous cell carcinoma cells via miR-506-5p/EIF5A/PTCH1 axis. Curr. Mol. Pharmacol. 2023 16 8 300123213257 10.2174/1874467216666230130132927 36717994
    [Google Scholar]
  21. Yee K.K. Li Y. Redding K.M. Iwatsuki K. Margolskee R.F. Jiang P. Lgr5-EGFP marks taste bud stem/progenitor cells in posterior tongue. Stem Cells 2013 31 5 992 1000 10.1002/stem.1338 23377989
    [Google Scholar]
  22. Shi F. Kempfle J.S. Edge A.S.B. Wnt-responsive Lgr5-expressing stem cells are hair cell progenitors in the cochlea. J. Neurosci. 2012 32 28 9639 9648 10.1523/JNEUROSCI.1064‑12.2012 22787049
    [Google Scholar]
  23. Ren W. Ma Z. Wang L. Feng X. Yu H. Yu Y. Lgr5 + cells are required and dynamically participate in olfactory epithelium regeneration: A revisiting shows Lgr5 expression in multiple cell lineages. Theranostics 2022 12 13 5631 5644 10.7150/thno.60636 35966594
    [Google Scholar]
  24. Fatuzzo I. Niccolini G.F. Zoccali F. Neurons, nose, and neurodegenerative diseases: Olfactory function and cognitive impairment. Int. J. Mol. Sci. 2023 24 3 2117 10.3390/ijms24032117 36768440
    [Google Scholar]
  25. Wu T. Li W. Zhuang L. Deficiency of aging‐related gene chitinase‐like 4 impairs olfactory epithelium homeostasis. Cell Prolif. 2025 58 8 70055 10.1111/cpr.70055 40389328
    [Google Scholar]
  26. Ikushima H. Suzuki J. Hemmi T. Effects of zinc deficiency on the regeneration of olfactory epithelium in mice. Chem. Senses 2023 48 bjad023 10.1093/chemse/bjad023 37527505
    [Google Scholar]
  27. Boucherat O. Boczkowski J. Jeannotte L. Delacourt C. Cellular and molecular mechanisms of goblet cell metaplasia in the respiratory airways. Exp. Lung Res. 2013 39 4-5 207 216 10.3109/01902148.2013.791733 23638644
    [Google Scholar]
  28. Kariyawasam H.H. Chronic rhinosinusitis with nasal polyps: Mechanistic insights from targeting IL-4 and IL-13 via IL-4Rα inhibition with dupilumab. Expert Rev. Clin. Immunol. 2020 16 12 1115 1125 10.1080/1744666X.2021.1847083 33148074
    [Google Scholar]
  29. Siddiqui S. Johansson K. Joo A. Epithelial miR-141 regulates IL-13–induced airway mucus production. JCI Insight 2021 6 5 139019 10.1172/jci.insight.139019 33682796
    [Google Scholar]
  30. Hellings P.W. Steelant B. Epithelial barriers in allergy and asthma. J. Allergy Clin. Immunol. 2020 145 6 1499 1509 10.1016/j.jaci.2020.04.010 32507228
    [Google Scholar]
  31. Zhai Z. Shao L. Lu Z. Characteristics of mucin hypersecretion in different inflammatory patterns based on endotypes of chronic rhinosinusitis. Clin. Transl. Allergy 2024 14 1 12334 10.1002/clt2.12334 38282195
    [Google Scholar]
  32. Moonwiriyakit A. Yimnual C. Noitem R. GPR120/FFAR4 stimulation attenuates airway remodeling and suppresses IL-4- and IL-13-induced airway epithelial injury via inhibition of STAT6 and Akt. Biomed. Pharmacother. 2023 168 115774 10.1016/j.biopha.2023.115774 37924784
    [Google Scholar]
  33. Wu Q. Xu X. Miao X. YAP signaling in horizontal basal cells promotes the regeneration of olfactory epithelium after injury. Stem Cell Reports 2022 17 3 664 677 10.1016/j.stemcr.2022.01.007 35148842
    [Google Scholar]
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The Role of Interleukin-4 in Olfactory Epithelial Cells: A Preliminary In Vitro Study
Bentham Science Publishers ; https://doi.org/10.2174/0115672026420545250911091301
/content/journals/cnr/10.2174/0115672026420545250911091301
/content/journals/cnr/10.2174/0115672026420545250911091301
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  • Article Type:     Research Article
Keywords: olfactory epithelium-like organoids ; olfactory function ; olfactory sensory neurons ; globular basal cells ; basal stem cells ; Interleukin-4

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