Laetitia Everaere1, Saliha Ait-Yahia2, Olivier Molendi-Coste3, Han Vorng2, Sandrine Quemener3, Pauline LeVu3, Sebastien Fleury3, Emmanuel Bouchaert3, Ying Fan2, Catherine Duez2, Patricia de Nadai2, Bart Staels3, David Dombrowicz4, Anne Tsicopoulos5. 1. 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. 2. 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. 3. 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. 4. 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. 5. 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.
Abstract
BACKGROUND: 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). OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: These results indicate that HFD-induced obesity might exacerbate allergic airway inflammation through mechanisms involving ILC2s and ILC3s.
BACKGROUND: 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). OBJECTIVE: 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. METHODS: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. RESULTS: HFD feeding exacerbated allergic airway disease features, including humoral response, airway and tissue eosinophilia, AHR, and TH2 and TH17 pulmonary profiles. Notably, nonsensitized obesemice 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 obesemice 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 obesemice, including TH2 and TH17 infiltration. CONCLUSION: These results indicate that HFD-induced obesity might exacerbate allergic airway inflammation through mechanisms involving ILC2s and ILC3s.
Authors: Bryan Simons; Maria E Ferrini; Sophia Carvalho; David J P Bassett; Zeina Jaffar; Kevan Roberts Journal: J Immunol Date: 2016-11-28 Impact factor: 5.422
Authors: Laurel A Monticelli; Joshua M Diamond; Steven A Saenz; Elia D Tait Wojno; Mary K Porteous; Edward Cantu; David Artis; Jason D Christie Journal: Am J Respir Crit Care Med Date: 2020-01-01 Impact factor: 21.405