Fig. 4: LCN2 specifically mediates NKp46⁺ILC3 ferroptosis susceptibility and functions in colitis through GPX4.

a Statistical results of MFI for LCN2 expression in LPMC-derived ILC3s (left) and CD4⁺RORγt⁺ cells (right) after in vivo ferroptosis intervention in mice infected with C.R. (n = 4) b Comparison of LCN2 expression in NKp46⁺ILC3, CCR6⁺ILC3, and DN cell subsets from LPMCs of WT mice after C.R infection. (n = 4) Lcn2^fl/fl and Rorc^creLcn2^fl/fl mice were orally administered with 1 × 10⁸ CFU of C.R, and their tissues were collected on Day 8 post-infection. c Representative spleen images and d statistical results of spleen weight of Lcn2^fl/fl and Rorc^creLcn2^fl/fl mice on day 8 post infection. (n = 4) e Representative H&E-stained colon sections from indicated mice with C.R infection (scale bars: 100 μm). f The statistical results of histological scores are shown. (n = 4) g Body weight changes of indicated mice. (n = 4) Log10 CFU of C.R in h liver and i spleen tissues from indicated mice on day 8 post infection. (n = 4) j The comparison of CD4⁺RORγt⁺ cell proportions (left) and absolute numbers (right) in LPMCs of Lcn2^fl/fl and Rorc^creLcn2^fl/fl mice post C.R infection. (n = 4) Statistical results of the proportion (left) and absolute number (right) of k ILC3s, including l NKp46⁺ILC3, m CCR6⁺ILC3, and n DN cell populations in LPMCs of the indicated mice after C.R infection. (n = 4) Statistical results of proportion (left) and numbers (right) of o IL-22-, and p IL-17A-positive ILC3s from LPMCs of indicated mice. (n = 4) q Statistical results of the proportion (left) and numbers (right) of neutrophils in LPMCs from the indicated mice. (n = 4) r Relative RegIIIβ and RegIIIγ mRNA expression in the colon tissue of the indicated mice. (n = 3) s Heatmap of differentially expressed genes related to ferroptosis in ILC3s from Lcn2^fl/fl and Rorc^creLcn2^fl/fl mice following C.R infection. t Relative expression of mRNA related to ferroptosis in ILC3s isolated from LPMCs of indicated mice. (n = 3) Statistical results of u the percentage of annexin V and 7-AAD double-negative population and v lipid ROS production in LPMC-derived ILC3s from the indicated mice. (n = 4) w Fe²⁺ level in ILC3s from LPMCs was analyzed using FerroOrange, and the statistical results are shown. (n = 4) Statistical results of x ATF4, y xCT, and z GPX4 expression in ILC3s from LPMCs of indicated mice. (n = 4) Data are presented as the mean ± SEM or median, and statistical significance was determined using two-sided unpaired t-test (a, b, d, f–r, t–z). *P < 0.05; **P < 0.01; ***P < 0.001.