12R-HETE acts as an endogenous ligand for Nur77 in the intestines and regulates NKp46⁺ ILC3 development.

ABSTRACT: How intestinal immunity develops during early life remains a key question in understanding defense against infections. Group 3 innate lymphoid cells (ILC3s) are critical for this defense, and their developmental progression and subset balance are essential for effective immune function. Here, we show that the nuclear receptor Nur77 helps control NKp46⁺ ILC3 development in newborn mice. Mice lacking Nur77 have fewer ILC3s and failed to convert one ILC3 subtype (NKp46^-) into a more protective form (NKp46⁺), reducing their ability to fight Salmonella enterica serovar Typhimurium infection. We found that 12R-hydroxyeicosatetraenoic acid (12R-HETE), a natural lipid found in the intestine, binds to Nur77 and boosts the expression of transcription factor T-

SUBMITTER: Huang N 

PROVIDER: S-EPMC12922749 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature