Disturbed LTB4 metabolism in ILC2 Aggravates Ulcerative Colitis via intercellular ATP accumulation

LTB4 biosynthesis is critically required for cytokine secretion by the group 2 innate lymphoid cell (ILC2), though its underlying regulatory mechanisms remain incompletely characterized. To investigate how LTB4 governs ILC2 functionality, we performed RNA sequencing on sorted murine colonic ILC2s treated with or without SC-57461A—an inhibitor targeting LTA4H, the key enzyme in LTB4 anabolism. This dataset delineates transcriptomic profiles of ILC2 with pharmacologically attenuated versus intact LTB4 synthesis. Here, we identify significant alterations in mitochondria-associated genes (including Fdps, Hmgcs1, and Acat3) upon suppression of LTB4 anabolism in ILC2. These genes encode proteins essential for mitochondrial function and are indispensable for ILC2 energy metabolism. These findings collectively demonstrate that LTB4 synthesis orchestrates mitochondrial functionality in ILC2, thereby modulating their bioenergetic capacity.RNA sequencing was performed for the SC-57461A- or vehicle-treated ILC2 sorted from the large intestine of C57BL/6 mice (n = 4 per group). Sorted large intestinal ILC2s from C57BL/6 mice were cultured in complete IMDM media containing IL-2 (10 ng/mL), IL-7 (10 ng/mL), IL-25 (10 ng/mL), and IL-33 (10 ng/mL) for 5 days, followed by treatment with SC-57461A for 16 hours. The SC-57461A- or vehicle-treated ILC2s were harvested by centrifugation and lysed for RNA extraction.