title: In vivo and in vitro studies of Th17 response to specific immunotherapy in house dust mite-induced allergic rhinitis patients.
abstract: T helper (Th)17 cells have been implicated in the development of allergic rhinitis (AR), but their response to specific immunotherapy (SIT) remains unclear. We investigated the impact of SIT on Th17 response and Th1/Th2 changes in AR patients. Blood samples from AR patients (n = 20) who were monosensitized to house dust mite (HDM) were collected before the initiation of SIT (SIT-untreated) and after the end of 2-year SIT (SIT-treated) treatment. Twenty healthy volunteers were recruited as controls. In vitro HDM stimulation in peripheral blood mononuclear cells (PBMCs) was also performed. Expression levels of Th17 associated genes were determined in both PBMCs and plasma by PCR and ELISA, while Th17/Th1/Th2/IL10 producing cell proportions were evaluated in PBMCs by flow cytometry. The SIT effect was evaluated by assessing clinical symptoms. mRNA levels of Th17 specific genes (IL17 and RORC) were increased in SIT-untreated AR versus controls, and decreased following SIT treatment. SIT can change the production of Th17 associated genes (reduction of IL17, IL6, and IL23, but increase of IL27) in plasma from AR patients. Th2/Th1 ratio and proportions of Th17 cells were suppressed while IL10 producing CD4+ T cells were elevated after SIT. In vitro HDM challenge presents concordant patterns with in vivo findings: 1) increase of Th2 and Th17 response in AR patients; 2) suppression of IL10 producing CD4+ T cells in SIT-untreated AR but elevation in SIT-treated AR patients. Most importantly, a positive correlation between IL17 mRNA/protein levels and clinical symptom scores was observed. SIT significantly inhibits Th17 mediated inflammation in AR and IL17 may be a useful biomarker for both AR severity and SIT therapeutic effect.
  
  
  BACKGROUND
  Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12613000445774.
authors.affiliation: Department of Otolaryngology, National University of Singapore, National University Health System, Singapore, Singapore.
authors.forename: Chun Wei
authors.initials: CW
authors.lastname: Li
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Department of Otolaryngology-Head and Neck Surgery, Shantou Central Hospital of Sun Yat-sen University, Shantou, China.
authors.forename: Han Gui
authors.initials: HG
authors.lastname: Lu
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Department of Allergy, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: De Hua
authors.initials: DH
authors.lastname: Chen
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Department of Allergy, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Zhi Bin
authors.initials: ZB
authors.lastname: Lin
authors.affiliation: Department of Otolaryngology, National University of Singapore, National University Health System, Singapore, Singapore.
authors.forename: De Yun
authors.initials: DY
authors.lastname: Wang
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Department of Allergy, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Tian Ying
authors.initials: TY
authors.lastname: Li
mesh_terms: D000328:Adult; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007109:Immunity; D007167:Immunotherapy; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D039981:Pyroglyphidae / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D065631:Rhinitis, Allergic / Q000235:genetics / Q000276:immunology* / Q000469:parasitology*; D058504:Th17 Cells / Q000276:immunology*; D064232:Visual Analog Scale
chemical_list: D016207:Cytokines; D012333:RNA, Messenger