title: Thymic stromal lymphopoietin activation of basophils in patients with allergic asthma is IL-3 dependent.
abstract: BACKGROUND
  Thymic stromal lymphopoietin (TSLP) released after antigenic stimulation of allergic asthmatic airways is a key initiator of type 2 inflammation. Basophils are important effectors of allergic inflammation in the airways. Murine basophils have been shown to respond to TSLP independently of IL-3 by increasing functional thymic stromal lymphopoietin receptor (TSLPR) expression.
  
  
  OBJECTIVE
  The purpose of this study was to investigate the effect of TSLP stimulation on human basophil function.
  
  
  METHODS
  Ten patients with mild allergic asthma underwent diluent and allergen inhalation challenges. Peripheral blood and sputum samples were collected at baseline and 7 and 24 hours after challenge, and bone marrow samples were collected at baseline and 24 hours after challenge to measure basophil TSLPR expression. In vitro experiments were conducted on purified human basophils to measure the effect of TSLP on degranulation, expression of activation markers and TH2 cytokines, and eotaxin-induced shape change.
  
  
  RESULTS
  Allergen inhalation increased basophil numbers in the airways and significantly upregulated the expression of activation markers, TH2 intracellular cytokines, and receptors for TSLP, IL-3, and eotaxin in blood, bone marrow, and sputum basophils. In vitro stimulation with TSLP primed basophil migration to eotaxin and induced rapid and sustained basophil activation mediated directly through TSLPR and indirectly through an IL-3-mediated basophil autocrine loop. Basophils responded to TSLP at a similar magnitude and potency as the well-described basophil-activating stimuli IL-3 and anti-IgE.
  
  
  CONCLUSIONS
  Our findings indicate that basophil activation during early- and late-phase responses to inhaled allergen might be driven at least in part by TSLP.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Brittany M
authors.initials: BM
authors.lastname: Salter
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: John Paul
authors.initials: JP
authors.lastname: Oliveria
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Graeme
authors.initials: G
authors.lastname: Nusca
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Steve G
authors.initials: SG
authors.lastname: Smith
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Rick M
authors.initials: RM
authors.lastname: Watson
authors.affiliation: Department of Inflammation Research, Amgen, Seattle, Wash.
authors.forename: Micheal
authors.initials: M
authors.lastname: Comeau
authors.affiliation: Firestone Institute for Respiratory Health, St Josephs, Hamilton, Ontario, Canada.
authors.forename: Roma
authors.initials: R
authors.lastname: Sehmi
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada. Electronic address: gauvreau@mcmaster.ca.
authors.forename: Gail M
authors.initials: GM
authors.lastname: Gauvreau
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000485:Allergens / Q000008:administration & dosage*; D001249:Asthma / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D001491:Basophils / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D001985:Bronchial Provocation Tests; D002452:Cell Count; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D013183:Sputum / Q000166:cytology / Q000276:immunology; D055815:Young Adult; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000485:Allergens; D016207:Cytokines; D000094632:Thymic Stromal Lymphopoietin
keywords: Basophils; CD203c; T(H)2 cytokines; allergic asthma; epithelium-derived cytokines; thymic stromal lymphopoietin