The Role of Innate Lymphoid Cells in Pulmonary Viral Infection and Allergic Inflammation
Stier, Matthew Tyler
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2017-08-30
Abstract
Airway inflammatory diseases including viral bronchiolitis and allergy are significant causes or morbidity and mortality worldwide. A recently identified lineage of leukocytes known as innate lymphoid cells (ILC) have potent inflammatory potential, but their mechanistic role in airway inflammation is not entirely understood. Group 2 ILC were identified to be activated in a mouse model of severe respiratory syncytial virus (RSV) infection and correlated with significant pathophysiologic changes in the airways including mucus production. That activation depended upon the cytokine thymic stromal lymphopoietin (TSLP). Broadly, group 1, 2, and 3 ILC responses were coordinated by signal transducer and activator of transcription 1 (STAT1), which promoted group 1 ILC and restricted group 2 and 3 ILC during RSV infection. Finally, IL-33 signaling mediated egress of ILC2 from the bone marrow during initial seeding of tissues in the post-natal period as well as in the context of allergic inflammation. These data broadly support a role for ILC2 in the pathogenesis of respiratory viral infection and provide mechanistic insights into how ILC2 egress from the bone marrow to support allergic inflammation.