Brittany M Salter1, John Paul Oliveria1, Graeme Nusca1, Steve G Smith1, Rick M Watson1, Micheal Comeau2, Roma Sehmi3, Gail M Gauvreau4. 1. Department of Medicine, McMaster University, Hamilton, Ontario, Canada. 2. Department of Inflammation Research, Amgen, Seattle, Wash. 3. Firestone Institute for Respiratory Health, St Josephs, Hamilton, Ontario, Canada. 4. Department of Medicine, McMaster University, Hamilton, Ontario, Canada. Electronic address: gauvreau@mcmaster.ca.
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. CONCLUSION: Our findings indicate that basophil activation during early- and late-phase responses to inhaled allergen might be driven at least in part by TSLP.
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. CONCLUSION: 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: Michelle T Graham; Sandra Andorf; Jonathan M Spergel; Talal A Chatila; Kari C Nadeau Journal: Curr Allergy Asthma Rep Date: 2016-10 Impact factor: 4.806
Authors: Peter Korosec; Paul J Turner; Mira Silar; Peter Kopac; Mitja Kosnik; Bernhard F Gibbs; Mohamed H Shamji; Adnan Custovic; Matija Rijavec Journal: J Allergy Clin Immunol Date: 2017-03-22 Impact factor: 10.793
Authors: Brittany M Salter; John Paul Oliveria; Graeme Nusca; Steve G Smith; Damian Tworek; Patrick D Mitchell; Rick M Watson; Roma Sehmi; Gail M Gauvreau Journal: Respir Res Date: 2016-01-14