Abstract：
The involvement of Group 3 innate lymphoid cells (ILC3s) and dendritic cells (DCs) in chronic lung inflammation has been increasingly regarded as the key to understand the inflammatory mechanisms of smoke-related chronic obstructive pulmonary disease (COPD). However, the mechanism underlying the engagement of both remains unclear. Our study aimed to explore NCR-ILC3 differentiation in the lungs of mice exposed to cigarette smoke (CS) and to further investigate whether DCs activated by CS exposure contribute to the differentiation of ILCs into NCR-ILC3s. The study involved both in vivo and in vitro experiments. In the former, the frequencies of lung NCR-ILC3s and NKp46-IL-17A+ ILCs and the expression of DCs, CD40, CD86, IL-23, and IL-1β quantified by flow cytometry were compared between CS-exposed mice and air-exposed mice. In the latter, NKp46-IL-17A+ ILC frequencies quantified by flow cytometry were compared after two cocultures, one involving lung CD45+Lin-CD127+ ILCs sorted from air-exposed mice and DCs sifted by CD11c magnetic beads from CS-exposed mice and another including identical CD45+Lin-CD127+ ILCs and DCs from air-exposed mice. The results indicated significant increases in the frequencies of NCR-ILC3s and NKp46-IL-17A+ ILCs; in the expression of DCs, CD40, CD86, IL-23, and IL-1β in CS-exposed mice; and in the frequency of NKp46-IL-17A+ ILCs after the coculture with DCs from CS-exposed mice. In conclusion, CS exposure increases the frequency of lung ILCs and NCR-ILC3s. CS-induced DC activation enhances the differentiation of ILCs into NCR-ILC3s, which likely acts as a mediating step in the involvement of NCR-ILC3s in chronic lung inflammation.
摘要：
第3组固有淋巴样细胞（ILC3s）和树突状细胞（DCs）参与慢性肺部炎症已越来越被认为是了解烟雾相关慢性阻塞性肺疾病（COPD）炎症机制的关键。然而,两者参与的潜在机制尚不清楚.我们的研究旨在探索暴露于香烟烟雾（CS）的小鼠肺部的NCR-ILC3分化，并进一步研究CS暴露激活的DC是否有助于ILC分化为NCR-ILC3。该研究涉及体内和体外实验。在前者中,肺NCR-ILC3s和NKp46-IL-17A+ILC的频率和DC的表达，在CS暴露的小鼠和空气暴露的小鼠之间比较了通过流式细胞术定量的CD40，CD86，IL-23和IL-1β。在后者中,在两次共培养后，比较了通过流式细胞术定量的NKp46-IL-17AILC频率，一个涉及从暴露于空气的小鼠中分选的肺CD45Lin-CD127ILC和通过来自暴露于CS的小鼠的CD11c磁珠筛选的DC，另一个涉及来自暴露于空气的小鼠的相同的CD45Lin-CD127ILC和DC。结果表明NCR-ILC3s和NKp46-IL-17A+ILC的频率显着增加；在DC的表达中，CS暴露小鼠中的CD40，CD86，IL-23和IL-1β；以及与CS暴露小鼠的DC共培养后NKp46-IL-17AILC的频率。总之,CS暴露增加了肺ILC和NCR-ILC3的频率。CS诱导的DC激活增强ILC分化为NCR-ILC3，这可能是NCR-ILC3参与慢性肺部炎症的介导步骤。
