Dendritic Cells Promote the Differentiation of ILCs into NCRILC3s in the Lungs of Mice Exposed to Cigarette Smoke.

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 NCRILC3 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 NCRILC3s. The study involved both and experiments. In the former, the frequencies of lung NCRILC3s and NKp46IL-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, NKp46IL-17A ILC frequencies quantified by flow cytometry were compared after two cocultures, one involving lung CD45LinCD127 ILCs sorted from air-exposed mice and DCs sifted by CD11c magnetic beads from CS-exposed mice and another including identical CD45LinCD127 ILCs and DCs from air-exposed mice. The results indicated significant increases in the frequencies of NCRILC3s and NKp46IL-17A ILCs; in the expression of DCs, CD40, CD86, IL-23, and IL-1β in CS-exposed mice; and in the frequency of NKp46IL-17A ILCs after the coculture with DCs from CS-exposed mice. In conclusion, CS exposure increases the frequency of lung ILCs and NCRILC3s. CS-induced DC activation enhances the differentiation of ILCs into NCRILC3s, which likely acts as a mediating step in the involvement of NCR-ILC3s in chronic lung inflammation.