ArticleJCI insight2024
DDIT4L regulates mitochondrial and innate immune activities in early life.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Maturation-Dependent Constraints in the Ability of Human Monocytes to Initiate Trained Immunity.MedComm · 2026Article
- Adipocyte Myoglobin Is a Determinant of Energy Expenditure and a Potential Target to Limit Obesity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- From homeostasis to dysregulation: human milk, microbial metabolites, and the preterm intestinal microenvironment in necrotizing enterocolitis.Translational pediatrics · 2026Review
- Acute wood smoke exposure is associated with cell-specific hippocampal transcriptomic responses in an accelerated ovarian failure mouse model.Neurotoxicology · 2026Article
- Antioxidant, Redox, and Immunomodulatory Effects ofBiomedicines · 2026Article
- GSK3β promotes p53/Nrf2-dependent expression of the stress response protein REDD2 in retinal Müller glia exposed to hyperlipidemic conditions.Experimental eye research · 2026Article
- Identification and validation of tumor microenvironment remodeling markers associated with prognosis in differentiated thyroid cancer.Translational cancer research · 2026Article
- Systems biology approaches to unravelling neonatal sepsis and potential for precision diagnostics and therapeutics.Frontiers in pharmacology · 2026Review
- Immune profiling in a living human recipient of a gene-edited pig kidney.Nature medicine · 2026Article
- Metabolite-driven protein modifications in immune signaling: from established principles to emerging pyruvylation.Frontiers in immunology · 2026Review
- m6A regulator-based molecular classification and hub genes associated with immune infiltration characteristics and clinical outcomes in diffuse gliomas.BMC medical genomics · 2025Article
- Mechanisms of host-bacterial interactions duringFrontiers in veterinary science · 2025Article
- Identifying shared diagnostic genes and mechanisms in vascular dementia and Alzheimer's disease via bioinformatics and machine learning.Journal of Alzheimer's disease reports · 2024Article
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Authors and funding
19 authors.
Funding
Abstract
Pattern recognition receptor responses are profoundly attenuated before the third trimester of gestation in the relatively low-oxygen human fetal environment. However, the mechanisms regulating these responses are uncharacterized. Herein, genome-wide transcription and functional metabolic experiments in primary neonatal monocytes linked the negative mTOR regulator DDIT4L to metabolic stress, cellular bioenergetics, and innate immune activity. Using genetically engineered monocytic U937 cells, we confirmed that DDIT4L overexpression altered mitochondrial dynamics, suppressing their activity, and blunted LPS-induced cytokine responses. We also showed that monocyte mitochondrial function is more restrictive in earlier gestation, resembling the phenotype of DDIT4L-overexpressing U937 cells. Gene expression analyses in neonatal granulocytes and lung macrophages in preterm infants confirmed upregulation of the DDIT4L gene in the early postnatal period and also suggested a potential protective role against inflammation-associated chronic neonatal lung disease. Taken together, these data show that DDIT4L regulates mitochondrial activity and provide what we believe to be the first direct evidence for its potential role supressing innate immune activity in myeloid cells during development.
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