Functional remodeling of iNKT cells by sulfatide-reactive type II NKT cells reprograms alveolar macrophages to alleviate lung ischemia-reperfusion injury.

ABSTRACT: Lung ischemia-reperfusion injury (LIRI) is a serious complication in critical clinical situations. Despite its importance, the specific role of type II natural killer T (NKT) cells in LIRI remains unclear. In this study, we establish a LIRI mouse model and demonstrate that sulfatide-reactive type II NKT cells promote M2 polarization of alveolar macrophages (AMs) and alleviate LIRI through AMs-mediated mechanisms. This protective effect is absent in Jα18^-/- mice, indicating the essential role of invariant NKT (iNKT) cells. Further analysis shows that interleukin-10 (IL-10) secreted by iNKT cells upregulates AT-rich interaction domain 3 A (Arid3a) in macrophages, which then promotes the transcription of DNA damage inducible transcript 4 (DDIT4). This cascade enhances M2 polarizati

SUBMITTER: Li Q 

PROVIDER: S-EPMC12923794 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature