RATIONALE: Activation of type 2 cytokine pathways plays a central role in a large subset of subjects with asthma. Th2-high and Th2-low asthma have distinct clinical, pathologic, and molecular phenotypes and respond differently to therapy. The factors that initiate type 2 responses in some subjects with asthma are unknown. OBJECTIVES: To determine whether expression of epithelial cytokines IL-25, IL-33, and thymic stromal lymphopoietin are associated with type 2 responses and predict response to inhaled corticosteroid (ICS) in asthma. METHODS: We analyzed pulmonary function tests, blood, and bronchoscopic biopsies from 21 healthy control subjects and 43 subjects with asthma. Subjects with asthma underwent an 8-week treatment with inhaled budesonide. MEASUREMENTS AND MAIN RESULTS: Epithelial expression of IL-25, but not IL-33 or thymic stromal lymphopoietin, was increased in a subset of subjects with asthma. The IL-25-high subset had greater airway hyperresponsiveness, more airway and blood eosinophils, higher serum IgE, more subepithelial thickening, and higher expression of Th2 signature genes. ICS improved FEV1 and hyperresponsiveness in the IL-25-high but not the IL-25-low subset. Plasma IL-25 levels correlated with epithelial IL-25 expression, airway eosinophilia, and beneficial responses to ICS treatment. CONCLUSIONS: IL-25 measurements identify two subsets of subjects with distinct asthma phenotypes and different responses to ICS. Because IL-25 has a major role in triggering type 2 responses, bronchial epithelial IL-25 expression is likely a key determinant of type 2 response activation in asthma. Plasma IL-25 level reflects airway IL-25/type 2 response activation and may be useful for predicting responses to asthma therapy.
RATIONALE: Activation of type 2 cytokine pathways plays a central role in a large subset of subjects with asthma. Th2-high and Th2-low asthma have distinct clinical, pathologic, and molecular phenotypes and respond differently to therapy. The factors that initiate type 2 responses in some subjects with asthma are unknown. OBJECTIVES: To determine whether expression of epithelial cytokines IL-25, IL-33, and thymic stromal lymphopoietin are associated with type 2 responses and predict response to inhaled corticosteroid (ICS) in asthma. METHODS: We analyzed pulmonary function tests, blood, and bronchoscopic biopsies from 21 healthy control subjects and 43 subjects with asthma. Subjects with asthma underwent an 8-week treatment with inhaled budesonide. MEASUREMENTS AND MAIN RESULTS: Epithelial expression of IL-25, but not IL-33 or thymic stromal lymphopoietin, was increased in a subset of subjects with asthma. The IL-25-high subset had greater airway hyperresponsiveness, more airway and blood eosinophils, higher serum IgE, more subepithelial thickening, and higher expression of Th2 signature genes. ICS improved FEV1 and hyperresponsiveness in the IL-25-high but not the IL-25-low subset. Plasma IL-25 levels correlated with epithelial IL-25 expression, airway eosinophilia, and beneficial responses to ICS treatment. CONCLUSIONS:IL-25 measurements identify two subsets of subjects with distinct asthma phenotypes and different responses to ICS. Because IL-25 has a major role in triggering type 2 responses, bronchial epithelial IL-25 expression is likely a key determinant of type 2 response activation in asthma. Plasma IL-25 level reflects airway IL-25/type 2 response activation and may be useful for predicting responses to asthma therapy.
Authors: Prescott G Woodruff; Barmak Modrek; David F Choy; Guiquan Jia; Alexander R Abbas; Almut Ellwanger; Laura L Koth; Joseph R Arron; John V Fahy Journal: Am J Respir Crit Care Med Date: 2009-05-29 Impact factor: 21.405
Authors: Sun Ying; Brian O'Connor; Jonathan Ratoff; Qiu Meng; Kirsty Mallett; David Cousins; Douglas Robinson; Guizhen Zhang; Jisheng Zhao; Tak H Lee; Chris Corrigan Journal: J Immunol Date: 2005-06-15 Impact factor: 5.422
Authors: Stanley J Szefler; Brenda R Phillips; Fernando D Martinez; Vernon M Chinchilli; Robert F Lemanske; Robert C Strunk; Robert S Zeiger; Gary Larsen; Joseph D Spahn; Leonard B Bacharier; Gordon R Bloomberg; Theresa W Guilbert; Gregory Heldt; Wayne J Morgan; Mark H Moss; Christine A Sorkness; Lynn M Taussig Journal: J Allergy Clin Immunol Date: 2005-02 Impact factor: 10.793
Authors: Stephen D Hurst; Tony Muchamuel; Daniel M Gorman; Jonathan M Gilbert; Theresa Clifford; Sylvia Kwan; Satish Menon; Brian Seymour; Craig Jackson; Ted T Kung; Joan K Brieland; Sandra M Zurawski; Richard W Chapman; Gerard Zurawski; Robert L Coffman Journal: J Immunol Date: 2002-07-01 Impact factor: 5.422
Authors: Michael Noonan; Phillip Korenblat; Sofia Mosesova; Heleen Scheerens; Joseph R Arron; Yanan Zheng; Wendy S Putnam; Merdad V Parsey; Sean P Bohen; John G Matthews Journal: J Allergy Clin Immunol Date: 2013-05-29 Impact factor: 10.793
Authors: Padraic G Fallon; Sarah J Ballantyne; Niamh E Mangan; Jillian L Barlow; Ayan Dasvarma; Duncan R Hewett; Ann McIlgorm; Helen E Jolin; Andrew N J McKenzie Journal: J Exp Med Date: 2006-04-10 Impact factor: 14.307
Authors: Nirav R Bhakta; Owen D Solberg; Christine P Nguyen; Cindy N Nguyen; Joseph R Arron; John V Fahy; Prescott G Woodruff Journal: Clin Transl Allergy Date: 2013-07-17 Impact factor: 5.871
Authors: Ryan M Dunn; Erik Lehman; Vernon M Chinchilli; Richard J Martin; Homer A Boushey; Elliot Israel; Monica Kraft; Stephen C Lazarus; Robert F Lemanske; Njira L Lugogo; Stephen P Peters; Christine A Sorkness; Stanley Szefler; Michael E Wechsler Journal: Am J Respir Crit Care Med Date: 2015-09-01 Impact factor: 21.405
Authors: Neil N Patel; Michael A Kohanski; Ivy W Maina; Alan D Workman; De'Broski R Herbert; Noam A Cohen Journal: Int Forum Allergy Rhinol Date: 2018-09-10 Impact factor: 3.858
Authors: Lin Li; Nicholas W Lukacs; Matthew A Schaller; Bryan Petersen; Alan P Baptist Journal: Ann Allergy Asthma Immunol Date: 2016-12 Impact factor: 6.347
Authors: Antonia Wallrapp; Samantha J Riesenfeld; Patrick R Burkett; Raja-Elie E Abdulnour; Jackson Nyman; Danielle Dionne; Matan Hofree; Michael S Cuoco; Christopher Rodman; Daneyal Farouq; Brian J Haas; Timothy L Tickle; John J Trombetta; Pankaj Baral; Christoph S N Klose; Tanel Mahlakõiv; David Artis; Orit Rozenblatt-Rosen; Isaac M Chiu; Bruce D Levy; Monika S Kowalczyk; Aviv Regev; Vijay K Kuchroo Journal: Nature Date: 2017-09-13 Impact factor: 49.962
Authors: José Guilherme F M Galvão; Luiz Henrique Agra Cavalcante-Silva; Deyse Cristina M Carvalho; Laércia Karla D P Ferreira; Talissa Mozzini Monteiro; Adriano Francisco Alves; Larissa Adilis M P Ferreira; Francisco Allysson A F Gadelha; Marcia Regina Piuvezam; Sandra Rodrigues-Mascarenhas Journal: Inflamm Res Date: 2017-09-13 Impact factor: 4.575