title: Increased numbers of activated group 2 innate lymphoid cells in the airways of patients with severe asthma and persistent airway eosinophilia.
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.
authors.affiliation: Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Smith
authors.affiliation: Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Guangzhou Institute of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.
authors.forename: Ruchong
authors.initials: R
authors.lastname: Chen
authors.affiliation: Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Melanie
authors.initials: M
authors.lastname: Kjarsgaard
authors.affiliation: Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Chynna
authors.initials: C
authors.lastname: Huang
authors.affiliation: Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: John-Paul
authors.initials: JP
authors.lastname: Oliveria
authors.affiliation: Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Paul M
authors.initials: PM
authors.lastname: O'Byrne
authors.affiliation: Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Gail M
authors.initials: GM
authors.lastname: Gauvreau
authors.affiliation: Institut universitaire de cardiologie et de pneumologie de Québec, Quebec City, Quebec, Canada.
authors.forename: Louis-Philippe
authors.initials: LP
authors.lastname: Boulet
authors.affiliation: Division of Pneumologie, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lemiere
authors.affiliation: Meakins-Christie Laboratories, Research Institute of the McGill University Health Center, Hamilton, Ontario, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Martin
authors.affiliation: Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada. Electronic address: parames@mcmaster.ca.
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Nair
authors.affiliation: Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada. Electronic address: sehmir@mcmaster.ca.
authors.forename: Roma
authors.initials: R
authors.lastname: Sehmi
mesh_terms: D000328:Adult; D001249:Asthma / Q000097:blood / Q000276:immunology*; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D018793:Interleukin-13 / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011657:Pulmonary Eosinophilia / Q000097:blood / Q000276:immunology*; D013183:Sputum / Q000166:cytology; D055815:Young Adult
chemical_list: C578095:IL13 protein, human; C508599:IL5 protein, human; D018793:Interleukin-13; D015848:Interleukin-5
keywords: Group 2 innate lymphoid cells; eosinophilic bronchitis; severe asthma