Activated Plasmacytoid Dendritic Cells regulate Type 2 Innate Lymphoid Cells-mediated Airway Hyperreactivity

Publication date: Available online 1 June 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Hadi Maazi, Homayon Banie, German Aleman, Nisheel Patel, Bowen Wang, Ishwarya Sankaranarayanan, Vipul Bhargava, Takahiro Sato, Gavin Lewis, Matteo Cesaroni, James Karras, Anuk Das, Pejman Soroosh, Omid Akbari
BackgroundAllergic asthma is a prevalent inflammatory disease of the airways caused by dysregulated immune balance in the lungs with incompletely understood pathogenesis. The recently identified type 2 innate lymphoid cells (ILC2s) play significant roles in the pathogenesis of asthma. While ILC2-activating factors have been identified, the mechanisms that suppress ILC2s remain largely unknown. Plasmacytoid dendritic cells, pDCs, are important in antiviral immunity and in maintaining tolerance to inert antigens.ObjectiveTo address the role of pDCs in regulating ILC2's function and ILC2-medited airway hyperreactivity (AHR) and lung inflammation.MethodsWe used several mouse models including BDCA-2-DTR transgenic and Interferon alpha receptor-1 deficient mice as well as purified primary ILC2s to reach our objective. We extended and validated our findings to human ILC2s.ResultsWe show that activation of pDCs through Toll-like receptor-7/8 suppresses ILC2-mediated AHR and airway inflammation and that depletion of pDCs reverses this suppression. We further show that pDCs suppress cytokine production and proliferation rate while increasing the apoptosis rate of ILC2s through the production of interferon alpha. Transcriptome analysis of both human and murine ILC2s confirms the activation of regulatory pathways in ILC2s by interferon alpha.ConclusionActivation of pDCs alleviates AHR and airway inflammation by suppressing ILC2's function and survival. Our findings reveal a novel regulatory pathway in ILC2-mediated pulmonary inflammation with important clinical implications.

Teaser

Capsule summary: pDCs suppress ILC2s through IFN-α


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