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Role of the type I tumor necrosis factor receptor in inflammation‐associated olfactory dysfunction
Author(s) -
Sousa Garcia Davi,
Chen Mengfei,
Smith Amy K.,
Lazarini Paulo Roberto,
Lane Andrew P.
Publication year - 2017
Publication title -
international forum of allergy and rhinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.503
H-Index - 46
eISSN - 2042-6984
pISSN - 2042-6976
DOI - 10.1002/alr.21855
Subject(s) - inflammation , medicine , olfactory epithelium , tumor necrosis factor alpha , knockout mouse , olfaction , olfactory system , tumor necrosis factor receptor 1 , pathology , proinflammatory cytokine , immunology , anosmia , receptor , neuroscience , biology , tumor necrosis factor receptor , disease , covid-19 , psychiatry , infectious disease (medical specialty)
Background To understand mechanisms of human olfactory dysfunction in chronic rhinosinusitis, an inducible olfactory inflammation (IOI) model has been utilized to chronically express inflammatory cytokines locally, resulting in neuronal loss, diminished odorant responses, and repressed olfactory regeneration. Knockout of the minor tumor necrosis factor α receptor 2 (TNFR2) was previously shown to partially rescue these olfactory changes. The purpose of current study was to investigate the role of the major TNF receptor, TNFR1, in chronic olfactory inflammation. Methods Two experimental groups of mice were studied: TNFR1 knockout in IOI background and TNFR1 knockout with allergen‐induced inflammation. Olfactory function was assayed by electro‐olfactogram (EOG), and olfactory tissue was processed for histology and immunohistochemical staining. Results TNF‐α was dramatically induced in IOI‐TNFR1 knockout mice, but the olfactory epithelium did not show inflammation. EOG responses were normal after either 2 or 8 weeks of TNF‐α expression. Ovalbumin‐sensitized TNFR1 knockout mice developed markedly diminished eosinophilic inflammatory infiltration. Conclusion Genetic deletion of TNFR1 completely blocks TNF‐α–induced inflammation and reduces allergen‐induced inflammation. Preserved EOG responses suggest a TNFR1‐dependent mechanism of TNF‐α–induced olfactory neuron dysfunction.