Matthew J Gold1, Frann Antignano1, Timotheus Y F Halim2, Jeremy A Hirota3, Marie-Renee Blanchet4, Colby Zaph5, Fumio Takei2, Kelly M McNagny6. 1. The Biomedical Research Centre, University of British Columbia, Vancouver. 2. Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver. 3. UBC James Hogg Research Centre, St Paul's Hospital, Vancouver. 4. Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Quebec City. 5. The Biomedical Research Centre, University of British Columbia, Vancouver; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver. 6. The Biomedical Research Centre, University of British Columbia, Vancouver. Electronic address: kelly@brc.ubc.ca.
Abstract
BACKGROUND: Allergic inflammation involves the sensitization of naive CD4(+) T cells to allergens, resulting in a TH2-skewed inflammatory response. Although antigen presentation by dendritic cells to T cells in the lymph node is crucial for TH2 cell development, the innate signals that initiate adaptive type 2 inflammation and the role of group 2 innate lymphoid cells (ILC2s) are poorly understood. OBJECTIVE: We sought to investigate the influence of ILC2s and the route of priming on the development of an adaptive type 2 immune response to lung allergens. METHODS: Wild-type and ILC2-deficient mice were exposed intranasally or systemically to the TH2-inducing antigens house dust mite or ovalbumin in a model of allergic airway inflammation or the TH17-inducing bacterial antigen Saccharopolyspora rectivirgula in a model of hypersensitivity pneumonitis. The formation of an adaptive immune response was evaluated based on serum antibody titers and production of T cell-derived cytokines (IL-4, IL-5, IL-13 and IL-17A). RESULTS: We find that lung ILC2s play a critical role in priming the adaptive type 2 immune response to inhaled allergens, including the recruitment of eosinophils, TH2 cytokine production and serum IgE levels. Surprisingly, systemic priming with ovalbumin, with or without adjuvants, circumvents the requirement for ILC2s in inducing TH2-driven lung inflammation. ILC2s were also found to be dispensable for the sensitization to TH1- or TH17-inducing antigens. CONCLUSION: These data highlight a critical role for ILC2s in the development of adaptive type 2 responses to local, but not systemic, antigen exposure.
BACKGROUND:Allergic inflammation involves the sensitization of naive CD4(+) T cells to allergens, resulting in a TH2-skewed inflammatory response. Although antigen presentation by dendritic cells to T cells in the lymph node is crucial for TH2 cell development, the innate signals that initiate adaptive type 2 inflammation and the role of group 2 innate lymphoid cells (ILC2s) are poorly understood. OBJECTIVE: We sought to investigate the influence of ILC2s and the route of priming on the development of an adaptive type 2 immune response to lung allergens. METHODS: Wild-type and ILC2-deficient mice were exposed intranasally or systemically to the TH2-inducing antigens house dust mite or ovalbumin in a model of allergic airway inflammation or the TH17-inducing bacterial antigen Saccharopolyspora rectivirgula in a model of hypersensitivitypneumonitis. The formation of an adaptive immune response was evaluated based on serum antibody titers and production of T cell-derived cytokines (IL-4, IL-5, IL-13 and IL-17A). RESULTS: We find that lung ILC2s play a critical role in priming the adaptive type 2 immune response to inhaled allergens, including the recruitment of eosinophils, TH2 cytokine production and serum IgE levels. Surprisingly, systemic priming with ovalbumin, with or without adjuvants, circumvents the requirement for ILC2s in inducing TH2-driven lung inflammation. ILC2s were also found to be dispensable for the sensitization to TH1- or TH17-inducing antigens. CONCLUSION: These data highlight a critical role for ILC2s in the development of adaptive type 2 responses to local, but not systemic, antigen exposure.
Authors: M J Gold; P R Hiebert; H Y Park; D Stefanowicz; A Le; M R Starkey; A Deane; A C Brown; G Liu; J C Horvat; Z A Ibrahim; M B Sukkar; P M Hansbro; C Carlsten; S VanEeden; D D Sin; K M McNagny; D A Knight; J A Hirota Journal: Mucosal Immunol Date: 2015-10-28 Impact factor: 7.313
Authors: Luan D Vu; David Siefker; Tamekia L Jones; Dahui You; Ryleigh Taylor; John DeVincenzo; Stephania A Cormier Journal: Am J Respir Crit Care Med Date: 2019-12-01 Impact factor: 21.405
Authors: Kazuki Furuhashi; Yen L Chua; Kenneth H S Wong; Qian Zhou; Debbie C P Lee; Ka H Liong; Guo H Teo; Paul E Hutchinson; David M Kemeny Journal: Immunology Date: 2017-04-03 Impact factor: 7.397
Authors: Sanhong Yu; Krystle M Leung; Hye-Young Kim; Sarah E Umetsu; Yanping Xiao; Lee A Albacker; Hyun-Jun Lee; Dale T Umetsu; Gordon J Freeman; Rosemarie H DeKruyff Journal: J Allergy Clin Immunol Date: 2019-01-29 Impact factor: 10.793