title: Innate lymphoid cells contribute to allergic airway disease exacerbation by obesity.
abstract: Epidemiologic and clinical observations identify obesity as an important risk factor for asthma exacerbation, but the underlying mechanisms remain poorly understood. Type 2 innate lymphoid cells (ILC2s) and type 3 innate lymphoid cells (ILC3s) have been implicated, respectively, in asthma and adipose tissue homeostasis and in obesity-associated airway hyperresponsiveness (AHR).
  
  
  
  We sought to determine the potential involvement of innate lymphoid cells (ILCs) in allergic airway disease exacerbation caused by high-fat diet (HFD)-induced obesity.
  
  
  
  Obesity was induced by means of HFD feeding, and allergic airway inflammation was subsequently induced by means of intranasal administration of house dust mite (HDM) extract. AHR, lung and visceral adipose tissue inflammation, humoral response, cytokines, and innate and adaptive lymphoid populations were analyzed in the presence or absence of ILCs.
  
  
  
  HFD feeding exacerbated allergic airway disease features, including humoral response, airway and tissue eosinophilia, AHR, and TH2 and TH17 pulmonary profiles. Notably, nonsensitized obese mice already exhibited increased lung ILC counts and tissue eosinophil infiltration compared with values in lean mice in the absence of AHR. The numbers of total and cytokine-expressing lung ILC2s and ILC3s further increased in HDM-challenged obese mice compared with those in HDM-challenged lean mice, and this was accompanied by high IL-33 and IL-1β levels and decreased ILC markers in visceral adipose tissue. Furthermore, depletion of ILCs with an anti-CD90 antibody, followed by T-cell reconstitution, led to a profound decrease in allergic airway inflammatory features in obese mice, including TH2 and TH17 infiltration.
  
  
  
  These results indicate that HFD-induced obesity might exacerbate allergic airway inflammation through mechanisms involving ILC2s and ILC3s.
authors.affiliation: Institut National de la Santé Et de la Recherche Médicale U1019, Lille, France; CNRS UMR 8204, Center for Infection and Immunity of Lille, Pulmonary Immunity Team, Lille, France; Institut Pasteur de Lille, Lille, France; Université de Lille, Lille, France; Institut National de la santé et de la recherche Médicale U1011, Lille, France; European Genomic Institute of Diabetes, Lille, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Everaere
authors.affiliation: Institut National de la Santé Et de la Recherche Médicale U1019, Lille, France; CNRS UMR 8204, Center for Infection and Immunity of Lille, Pulmonary Immunity Team, Lille, France; Institut Pasteur de Lille, Lille, France; Université de Lille, Lille, France.
authors.forename: Saliha
authors.initials: S
authors.lastname: Ait-Yahia
authors.affiliation: Institut Pasteur de Lille, Lille, France; Université de Lille, Lille, France; Institut National de la santé et de la recherche Médicale U1011, Lille, France; European Genomic Institute of Diabetes, Lille, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Molendi-Coste
authors.affiliation: Institut National de la Santé Et de la Recherche Médicale U1019, Lille, France; CNRS UMR 8204, Center for Infection and Immunity of Lille, Pulmonary Immunity Team, Lille, France; Institut Pasteur de Lille, Lille, France; Université de Lille, Lille, France.
authors.forename: Han
authors.initials: H
authors.lastname: Vorng
authors.affiliation: Institut Pasteur de Lille, Lille, France; Université de Lille, Lille, France; Institut National de la santé et de la recherche Médicale U1011, Lille, France; European Genomic Institute of Diabetes, Lille, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Quemener
authors.affiliation: Institut Pasteur de Lille, Lille, France; Université de Lille, Lille, France; Institut National de la santé et de la recherche Médicale U1011, Lille, France; European Genomic Institute of Diabetes, Lille, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: LeVu
authors.affiliation: Institut Pasteur de Lille, Lille, France; Université de Lille, Lille, France; Institut National de la santé et de la recherche Médicale U1011, Lille, France; European Genomic Institute of Diabetes, Lille, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Fleury
authors.affiliation: Institut Pasteur de Lille, Lille, France; Université de Lille, Lille, France; Institut National de la santé et de la recherche Médicale U1011, Lille, France; European Genomic Institute of Diabetes, Lille, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bouchaert
authors.affiliation: Institut National de la Santé Et de la Recherche Médicale U1019, Lille, France; CNRS UMR 8204, Center for Infection and Immunity of Lille, Pulmonary Immunity Team, Lille, France; Institut Pasteur de Lille, Lille, France; Université de Lille, Lille, France.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Institut National de la Santé Et de la Recherche Médicale U1019, Lille, France; CNRS UMR 8204, Center for Infection and Immunity of Lille, Pulmonary Immunity Team, Lille, France; Institut Pasteur de Lille, Lille, France; Université de Lille, Lille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Duez
authors.affiliation: Institut National de la Santé Et de la Recherche Médicale U1019, Lille, France; CNRS UMR 8204, Center for Infection and Immunity of Lille, Pulmonary Immunity Team, Lille, France; Institut Pasteur de Lille, Lille, France; Université de Lille, Lille, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: de Nadai
authors.affiliation: Institut Pasteur de Lille, Lille, France; Université de Lille, Lille, France; Institut National de la santé et de la recherche Médicale U1011, Lille, France; European Genomic Institute of Diabetes, Lille, France.
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.affiliation: Institut Pasteur de Lille, Lille, France; Université de Lille, Lille, France; Institut National de la santé et de la recherche Médicale U1011, Lille, France; European Genomic Institute of Diabetes, Lille, France. Electronic address: david.dombrowicz@pasteur-lille.fr.
authors.forename: David
authors.initials: D
authors.lastname: Dombrowicz
authors.affiliation: Institut National de la Santé Et de la Recherche Médicale U1019, Lille, France; CNRS UMR 8204, Center for Infection and Immunity of Lille, Pulmonary Immunity Team, Lille, France; Institut Pasteur de Lille, Lille, France; Université de Lille, Lille, France; Clinique des Maladies Respiratoires et Centre Hospitalier Régional et Universitaire de Lille, Lille, France. Electronic address: anne.tsicopoulos@pasteur-lille.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Tsicopoulos
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D001249:Asthma / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D016207:Cytokines / Q000276:immunology; D059305:Diet, High-Fat; D007113:Immunity, Innate; D007073:Immunoglobulin E / Q000097:blood; D008168:Lung / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D013154:Spleen / Q000166:cytology
chemical_list: D039741:Antigens, Dermatophagoides; D016207:Cytokines; D007073:Immunoglobulin E
keywords: Innate lymphoid cells; T(H)17; T(H)2; allergy; asthma; high-fat diet; house dust mite; obesity