title: Interleukin-25 and mucosal T cells in noneosinophilic and eosinophilic chronic rhinosinusitis.
abstract: BACKGROUND
  Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease of uncertain pathogenesis. Memory T cells acquire additional functions during the secondary response and play important roles in chronic inflammation.
  
  
  OBJECTIVE
  To investigate characteristics of tissue memory CD4(+) T cells obtained from patients with noneosinophilic CRSwNP (NECRS) and eosinophilic CRSwNP (ECRS) by focusing on the influence of interleukin (IL)-25.
  
  
  METHODS
  Pro-allergic cytokines in tissue homogenates were measured using enzyme-linked immunosorbent assays. NP mononuclear cells and CD4(+) T cells were isolated from NPs from patients with CRSwNP. Cytokine expression and CD4(+) T-cell subpopulations were analyzed using enzyme-linked immunosorbent assay, flow cytometry, and real-time polymerase chain reaction.
  
  
  RESULTS
  The IL-25 level in NPs increased in patients with ECRS. IL-5 and IL-9 mRNA levels expressed by tissue CD4(+) T cells were significantly elevated in patients with ECRS. Most infiltrating CD4(+) T cells in ECRS and NECRS expressed CD45RO; however, regardless of the atopic status, high IL-17RB levels were detected in CD4(+) T cells from patients with ECRS. IL-17RB mRNA levels expressed by tissue CD4(+) T cells significantly correlated with the number of eosinophils in NPs. Elevation of IL-5 and IL-9 production was found in NP mononuclear cells from patients with ECRS, but not in those from patients with NECRS, by stimulation with IL-25 under T-cell receptor stimulation.
  
  
  CONCLUSIONS
  Interleukin-25 and a subpopulation of tissue T-helper type 2 and 9 cells that express increased IL-17RB levels could contribute to infiltration of eosinophils in NPs and could have produced the pathologic difference between NECRS and ECRS.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan; Department of Advanced Allergology of the Airway, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Iinuma
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan. Electronic address: yokamoto@faculty.chiba-u.jp.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Okamoto
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Heizaburo
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Inamine-Sasaki
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ohki
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Toshioki
authors.initials: T
authors.lastname: Sakurai
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Urara
authors.initials: U
authors.lastname: Funakoshi
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Syuji
authors.initials: S
authors.lastname: Yonekura
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Daiju
authors.initials: D
authors.lastname: Sakurai
authors.affiliation: Department of Advanced Allergology of the Airway, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hirahara
authors.affiliation: Department of Immunology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000276:immunology*; D015848:Interleukin-5 / Q000276:immunology; D016906:Interleukin-9 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D009298:Nasal Polyps / Q000276:immunology*; D012220:Rhinitis / Q000276:immunology*; D012852:Sinusitis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D016207:Cytokines; C486701:IL25 protein, human; D020381:Interleukin-17; D015848:Interleukin-5; D016906:Interleukin-9