Activated plasmacytoid dendritic cells regulate type 2 innate lymphoid cell-mediated airway hyperreactivity

作者：Maazi Hadi; Banie Homayon; Muench German R Aleman; Patel Nisheel; Wang Bowen; Sankaranarayanan Ishwarya; Bhargava Vipul; Sato Takahiro; Lewis Gavin; Cesaroni Matteo; Karras James; Das Anuk; Soroosh Pejman; Akbari Omid^*

来源：Journal of Allergy and Clinical Immunology, 2018, 141(3): 893-+.

DOI：10.1016/j.jaci.2017.04.043

• Type 2 innate lymphoid cells
• asthma
• plasmacytoid dendritic cells
• eosinophilic airway inflammation
• immune regulation

Background: Allergic 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. Although 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.
Objective: We sought to address the role of pDCs in regulating ILC2 function and ILC2-mediated airway hyperreactivity (AHR) and lung inflammation.
Methods: We used several murine models, including BDCA-2-diphtheria toxin receptor (DTR) transgenic and IFN-alpha receptor 1-deficient mice, as well as purified primary ILC2s, to reach our objective. We extended and validated our findings to human ILC2s.
Results: We 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 the proliferation rate while increasing the apoptosis rate of ILC2s through IFN-alpha production. Transcriptomic analysis of both human and murine ILC2s confirms the activation of regulatory pathways in ILC2s by IFN-alpha.
Conclusion: Activation of pDCs alleviates AHR and airway inflammation by suppressing ILC2 function and survival. Our findings reveal a novel regulatory pathway in ILC2-mediated pulmonary inflammation with important clinical implications.

• 出版日期2018-3