Receptor for advanced glycation endproducts mediates allergic airway inflammation via group 2 innate lymphoid cells

摘要: Half of all asthmatics suffer from allergic airway inflammation driven by type 2 immune responses in the lung, yet molecular mechanisms that control early, initiating events asthma are poorly understood. Recently, scientists have discovered a new subset innate cells can trigger rapid inflammation, even absence an adaptive system. These cells, termed group lymphoid (ILC2s), activated epithelial alarmin, interleukin (IL)-33, and secrete copious amounts cytokines IL-5 IL-13 to drive tissue eosinophilia, mucus hypersecretion, hyperresponsiveness (AHR). It is unknown how these recruited lung promote (AAI). The receptor for advanced glycation endproducts (RAGE) proinflammatory abundantly expressed lung. Previous studies found that, RAGE, cytokine impaired, mouse lungs completely protected development AAI AHR. was therefore hypothesized RAGE necessary recruitment type-2-cytokine-producing ILC2s during allergen challenge initiate AAI. The data presented here demonstrate is, fact, ILC2 accumulation after challenge. Furthermore, this mechanism appears be lung-specific independent expression on themselves: tissues do not normally express (i.e. gastrointestinal tract) mount normal ILC2-driven KO mice. The ILC2-activating cytokine, IL-33, also dependent signaling, both upstream its release downstream mediate inflammatory effects. This first study examining parenchymal factor specific organ. exact which occurring still under investigation, but it may lead discovery important therapeutic targets early AAI.