title: Regulation of inflammation-associated olfactory neuronal death and regeneration by the type II tumor necrosis factor receptor.
abstract: BACKGROUND
  Olfactory loss is a debilitating symptom of chronic rhinosinusitis. To study the impact of inflammation on the olfactory system, the inducible olfactory inflammation (IOI) transgenic mouse was created in which inflammation can be turned on and off within the olfactory epithelium. In this study, the type II tumor necrosis factor (TNF) receptor (TNFR2) was knocked out, and the effect on the olfactory loss phenotype was assessed.
  
  
  METHODS
  IOI mice were bred to TNFR2 knockout mice to yield progeny IOI mice lacking the TNFR2 receptor (TNFR2(-/-) ). TNF-α expression was induced within the olfactory epithelium for 6 weeks to generate chronic inflammation. Olfactory function was assayed by electro-olfactogram (EOG), and olfactory tissue was processed for histology and immunohistochemical staining.
  
  
  RESULTS
  Compared to IOI mice with wild-type TNFR2, IOI mice lacking the TNFR2 demonstrated similar levels of inflammatory infiltration and enlargement of the subepithelial layer. However, IOI-TNFR2(-/-) mice differed markedly in that the neuronal layer was largely preserved and active progenitor cell proliferation was present. Odorant responses were maintained in the IOI-TNFR2(-/-) mice, in contrast to IOI mice.
  
  
  CONCLUSIONS
  TNFR2 is the minor receptor for TNF-α, but appears to play an important role in mediating TNF-induced disruption of the olfactory system. This finding suggests that neuronal death and inhibition of proliferation in CRS may be mediated by TNFR2 on olfactory neurons and progenitor cells. Further studies are needed to elucidate the subcellular pathways involved and develop novel therapies for treating olfactory loss in the setting of CRS.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Pozharskaya
authors.forename: Jonathan
authors.initials: J
authors.lastname: Liang
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Lane
mesh_terms: D000818:Animals; D016923:Cell Death / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D002908:Chronic Disease; D006801:Humans; D007249:Inflammation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D000857:Olfaction Disorders / Q000276:immunology / Q000503:physiopathology*; D009831:Olfactory Mucosa / Q000276:immunology*; D018034:Olfactory Receptor Neurons / Q000276:immunology*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000378:metabolism*; D012220:Rhinitis / Q000276:immunology / Q000503:physiopathology*; D012852:Sinusitis / Q000276:immunology / Q000503:physiopathology*; D012903:Smell / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha
keywords: TNF-alpha; TNFR2; olfactory loss; rhinosinusitis; transgenic model