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

ABSTRACT: 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).

ORGANISM(S): Mus musculus

PROVIDER: GSE304475 | GEO | 2025/08/12

REPOSITORIES: GEO

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Project description:Background: Salinity is an important abiotic stress that influences the physiological and metabolic activity, reproduction, growth and development of marine fish. It has been suggested that half-smooth tongue sole (Cynoglossus semilaevis), a euryhaline fish species, use a large amount of energy to maintain osmotic pressure balance when exposed to fluctuations in salinity. To delineate the molecular response of C. semilaevis to different levels of salinity, we performed RNA-seq analysis of the liver to identify the genes and molecular and biological processes involved in responding to salinity change. Results: The present study yielded 330.4 million clean reads, of which 83.9% were successfully mapped to the reference genome of C. semilaevis. One hundred twenty-eight differentially expressed genes (DEGs), including 43 up-regulated genes and 85 down-regulated genes, were identified. These DEGs were highly represented in metabolic pathways, steroid biosynthesis, terpenoid backbone biosynthesis, butanoate metabolism, glycerolipid metabolism and the 2-oxocarboxylic acid metabolism pathway. In addition, genes involved in metabolism, osmoregulation and ion transport, signal transduction, immune response and stress response, cytoskeleton remodeling, and apoptosis were affected during acclimation to low salinity. Genes acat2, fdps, hmgcr, hmgcs1, mvk, pmvk, ebp, lss, dhcr7, and dhcr24 were up-regulated and abat, ddc, acy1 were down-regulated in metabolic pathways. Genes aqp10 and slc6a6 were down-regulated in osmoregulation and ion transport. Genes abat, fdps, hmgcs1, mvk, pmvk and dhcr7 were first reported to be associated with salinity adaptation in teleosts. Conclusions: Our results revealed that metabolic pathways, especially lipid metabolism were important for salinity adaptation. The candidate genes identified from this study provide a basis for further studies to investigate the molecular mechanism of salinity adaptation and transcriptional plasticity in marine fish.

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

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