技术资料

Group 2 innate lymphoid cells (ILC2s) in the lung are stimulated by inhaled allergens. ILC2s do not directly recognize allergens but they are stimulated by cytokines including interleukin (IL)-33 released by damaged epithelium. In response to allergens,lung ILC2s produce T helper 2 cell type cytokines inducing T cell-independent allergic lung inflammation. Here we examined the fate of lung ILC2s upon allergen challenges. ILC2s proliferated and secreted cytokines upon initial stimulation with allergen or IL-33,and this phase was followed by a contraction phase as cytokine production ceased. Some ILC2s persisted long after the resolution of the inflammation as allergen-experienced ILC2s and responded to unrelated allergens more potently than naive ILC2s,mediating severe allergic inflammation. The allergen-experienced ILC2s exhibited a gene expression profile similar to that of memory T cells. The memory-like properties of allergen-experienced ILC2s may explain why asthma patients are often sensitized to multiple allergens. View Publication

Allergic asthma is a complex and chronic inflammatory disorder that is associated with airway hyperreactivity (AHR) and driven by Th2 cytokine secretion. Type 2 innate lymphoid cells (ILC2s) produce large amounts of Th2 cytokines and contribute to the development of AHR. Here,we show that ILC2s express the $\alpha$7-nicotinic acetylcholine receptor ($\alpha$7nAChR),which is thought to have an anti-inflammatory role in several inflammatory diseases. We show that engagement of a specific agonist with $\alpha$7nAChR on ILC2s reduces ILC2 effector function and represses ILC2-dependent AHR,while decreasing expression of ILC2 key transcription factor GATA-3 and critical inflammatory modulator NF-$\kappa$B,and reducing phosphorylation of upstream kinase IKK$\alpha$/$\beta$. Additionally,the specific $\alpha$7nAChR agonist reduces cytokine production and AHR in a humanized ILC2 mouse model. Collectively,our data suggest that $\alpha$7nAChR expressed by ILC2s is a potential therapeutic target for the treatment of ILC2-mediated asthma. View Publication