Group 2 innate lymphoid cells facilitate sensitization to local, but not systemic, TH 2-inducing allergen exposures

Background Allergic inflammation involves the sensitization of naive CD4+ T cells to allergens, resulting in a TH 2-skewed inflammatory response. Although antigen presentation by dendritic cells to T cells in the lymph node is crucial for TH 2 cell development, the innate signals that initiate adapt...

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Bibliographic Details
Published in:Journal of allergy and clinical immunology 2014, Vol.133 (4), p.1142-1148.e5
Main Authors: Gold, Matthew J., BSc, Antignano, Frann, PhD, Halim, Timotheus Y.F., PhD, Hirota, Jeremy A., PhD, Blanchet, Marie-Renee, PhD, Zaph, Colby, PhD, Takei, Fumio, PhD, McNagny, Kelly M., PhD
Format: Article
Language:English
Subjects:
Allergy and Immunology
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Summary:Background Allergic inflammation involves the sensitization of naive CD4+ T cells to allergens, resulting in a TH 2-skewed inflammatory response. Although antigen presentation by dendritic cells to T cells in the lymph node is crucial for TH 2 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 TH 2-inducing antigens house dust mite or ovalbumin in a model of allergic airway inflammation or the TH 17-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, TH 2 cytokine production and serum IgE levels. Surprisingly, systemic priming with ovalbumin, with or without adjuvants, circumvents the requirement for ILC2s in inducing TH 2-driven lung inflammation. ILC2s were also found to be dispensable for the sensitization to TH 1- or TH 17-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.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2014.02.033