Steven G Smith1, Ruchong Chen2, Melanie Kjarsgaard1, Chynna Huang1, John-Paul Oliveria1, Paul M O'Byrne1, Gail M Gauvreau1, Louis-Philippe Boulet3, Catherine Lemiere4, James Martin5, Parameswaran Nair6, Roma Sehmi7. 1. Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada. 2. Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Guangzhou Institute of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China. 3. Institut universitaire de cardiologie et de pneumologie de Québec, Quebec City, Quebec, Canada. 4. Division of Pneumologie, University of Montreal, Montreal, Quebec, Canada. 5. Meakins-Christie Laboratories, Research Institute of the McGill University Health Center, Hamilton, Ontario, Canada. 6. Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada. Electronic address: parames@mcmaster.ca. 7. Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada. Electronic address: sehmir@mcmaster.ca.
Abstract
BACKGROUND: In patients with severe eosinophilic asthma, local maturation rather than systemic recruitment of mature cells might contribute to persistent airway eosinophilia. Group 2 innate lymphoid cells (ILC2s) are a major source of type 2 cytokines (IL-5 and IL-13) and can facilitate eosinophilic inflammatory responses in mouse models of asthma in the absence of CD4+ lymphocytes. This study investigated the potential role of ILC2s in driving chronic airway eosinophilia in patients with severe asthma, despite regular high-dose oral corticosteroid therapy. METHODS: In a cross-sectional study we enumerated blood and sputum ILC2s (lin(-)CD45(+)127(+)ST2(+)) and levels of intracellular IL-5 and IL-13 in patients with severe asthma (n = 25), patients with steroid-naive mild atopic asthma (n = 19), and nonatopic control subjects (n = 5). Results were compared with numbers of CD4+ lymphocytes, eosinophil lineage-committed progenitors (eosinophilopoietic progenitor cells [EoPs]), and mature eosinophils. RESULTS: Significantly greater numbers of total and type 2 cytokine-producing ILC2s were detected in blood and sputum of patients with severe asthma compared to mild asthmatics. In contrast, intracellular cytokine expression by CD4 cells and EoPs within the airways did not differ between the asthmatic groups. In patients with severe asthma, although sputum CD4+ cells were more abundant than ILC2s and EoPs, proportionally, ILC2s were the predominant source of type 2 cytokines. In addition, there were significantly greater numbers of sputum IL-5(+)IL-13(+) ILC2s in patients with severe asthma whose airway eosinophilia was greater than 3%, despite normal blood eosinophil numbers (<300/μL). CONCLUSIONS: Our findings suggest that ILC2s can promote the persistence of airway eosinophilia in patients with severe asthma through uncontrolled localized production of the type 2 cytokines IL-5 and IL-13, despite high-dose oral corticosteroid therapy.
BACKGROUND: In patients with severe eosinophilic asthma, local maturation rather than systemic recruitment of mature cells might contribute to persistent airway eosinophilia. Group 2 innate lymphoid cells (ILC2s) are a major source of type 2 cytokines (IL-5 and IL-13) and can facilitate eosinophilic inflammatory responses in mouse models of asthma in the absence of CD4+ lymphocytes. This study investigated the potential role of ILC2s in driving chronic airway eosinophilia in patients with severe asthma, despite regular high-dose oral corticosteroid therapy. METHODS: In a cross-sectional study we enumerated blood and sputum ILC2s (lin(-)CD45(+)127(+)ST2(+)) and levels of intracellular IL-5 and IL-13 in patients with severe asthma (n = 25), patients with steroid-naive mild atopic asthma (n = 19), and nonatopic control subjects (n = 5). Results were compared with numbers of CD4+ lymphocytes, eosinophil lineage-committed progenitors (eosinophilopoietic progenitor cells [EoPs]), and mature eosinophils. RESULTS: Significantly greater numbers of total and type 2 cytokine-producing ILC2s were detected in blood and sputum of patients with severe asthma compared to mild asthmatics. In contrast, intracellular cytokine expression by CD4 cells and EoPs within the airways did not differ between the asthmatic groups. In patients with severe asthma, although sputum CD4+ cells were more abundant than ILC2s and EoPs, proportionally, ILC2s were the predominant source of type 2 cytokines. In addition, there were significantly greater numbers of sputum IL-5(+)IL-13(+) ILC2s in patients with severe asthma whose airway eosinophilia was greater than 3%, despite normal blood eosinophil numbers (<300/μL). CONCLUSIONS: Our findings suggest that ILC2s can promote the persistence of airway eosinophilia in patients with severe asthma through uncontrolled localized production of the type 2 cytokines IL-5 and IL-13, despite high-dose oral corticosteroid therapy.
Authors: Erin D Gordon; Laura J Simpson; Cydney L Rios; Lando Ringel; Marrah E Lachowicz-Scroggins; Michael C Peters; Agata Wesolowska-Andersen; Jeanmarie R Gonzalez; Hannah J MacLeod; Laura S Christian; Shaopeng Yuan; Liam Barry; Prescott G Woodruff; K Mark Ansel; Karl Nocka; Max A Seibold; John V Fahy Journal: Proc Natl Acad Sci U S A Date: 2016-07-18 Impact factor: 11.205
Authors: Jacqueline-Yvonne Cephus; Matthew T Stier; Hubaida Fuseini; Jeffrey A Yung; Shinji Toki; Melissa H Bloodworth; Weisong Zhou; Kasia Goleniewska; Jian Zhang; Sarah L Garon; Robert G Hamilton; Vasiliy V Poloshukin; Kelli L Boyd; R Stokes Peebles; Dawn C Newcomb Journal: Cell Rep Date: 2017-11-28 Impact factor: 9.423
Authors: Carlo De Salvo; Xiao-Ming Wang; Luca Pastorelli; Benedetta Mattioli; Sara Omenetti; Kristine A Buela; Saleem Chowdhry; Rekha R Garg; Wendy A Goodman; Alex Rodriguez-Palacios; Dirk E Smith; Derek W Abbott; Fabio Cominelli; Giorgos Bamias; Wei Xin; James J Lee; Maurizio Vecchi; Theresa T Pizarro Journal: Am J Pathol Date: 2016-02-22 Impact factor: 4.307
Authors: Franz Puttur; Laura Denney; Lisa G Gregory; Juho Vuononvirta; Robert Oliver; Lewis J Entwistle; Simone A Walker; Mark B Headley; Ewan J McGhee; James E Pease; Matthew F Krummel; Leo M Carlin; Clare M Lloyd Journal: Sci Immunol Date: 2019-06-07
Authors: Elizabeth A Kelly; Stephane Esnault; Lin Ying Liu; Michael D Evans; Mats W Johansson; Sameer Mathur; Deane F Mosher; Loren C Denlinger; Nizar N Jarjour Journal: Am J Respir Crit Care Med Date: 2017-12-01 Impact factor: 21.405