II型固有淋巴细胞通过粒细胞-巨噬细胞集落刺激因子编程肺部适应性免疫

Background: Group 2 innate lymphoid cells (ILC2s) and CD4+ TH2 cells are the cores of type 2 immunity in the lungs and play central roles in the pathology of asthma. ILC2s rapidly produce innate type 2 cytokines in response to environmental allergens, whereas TH2 cells provide adaptive antigen-specific immune memory. However, little is known regarding the interaction between the innate and adaptive arms of type 2 immunity. Objective: We investigated the roles of ILC2s in establishing adaptive antigen-specific immunity in a mouse model of human asthma. Methods: ILC2-deficient mice were intranasally sensitized to ovalbumin (OVA) using Alternaria extract as an adjuvant. Innate and adaptive responses were assessed by flow cytometry and by intranasal OVA recall challenge. The underlying mechanisms were investigated using gene-deficient mice, in vivo antibody neutralization, adoptive transfer of ILC2s, and in vitro culture systems. Results: Exposure of naive mice to the fungal allergen Alternaria increased the number of lung dendritic cells (DCs), activated migratory DCs, and promoted DC production of the TH2-recruiting chemokines CCL17 and CCL22; these responses were significantly suppressed in ILC2-deficient mice. Consequently, ILC2-deficient mice failed to develop TH2-type tissue-resident memory CD4+ T cells in the lungs and antigen-induced type 2 airway inflammation, which were restored by adoptive transfer of lung ILC2s. Granulocyte-macrophage colony-stimulating factor produced by ILC2s was indispensable in promoting these DC responses and development of lung tissue-resident memory T cells. Conclusion: ILC2s license lung DCs via granulocyte-macrophage colony-stimulating factor to prime and recruit TH2 cells, establishing antigen-specific T-cell immune memory in the lungs.