ArticleExperimental & molecular medicine2019
The transcription factor NFIL3 controls regulatory T-cell function and stability.
Article in Experimental & molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 62 citations in OpenAlex.
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- Circadian clocks and adaptive immune function: from mechanisms to therapeutic applications.Frontiers in immunology · 2025Review
- Focal adhesion kinase plays an essential role in Th17 cell differentiation by stimulating NF-κB signaling.Frontiers in immunology · 2025Article
- Methylation patterns at the adjacent CpG sites within enhancers are a part of cell identity.Epigenetics & chromatin · 2024Article
- Ferroptosis and inflammation are modulated by the NFIL3-ACSL4 axis in sepsis associated-acute kidney injury.Cell death discovery · 2024Article
- Circadian rhythms in solid organ transplantation.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2024Review
- Lupus susceptibility geneScience advances · 2024Article
- NFIL3 contributes to cytotoxic T lymphocyte-mediated killing.Open biology · 2024Article
- Circadian immunity from bench to bedside: a practical guide.The Journal of clinical investigation · 2024Review
- Transcriptional determinants of lipid mobilization in human adipocytes.Science advances · 2024Article
- The Inflammation-Induced Dysregulation of Reelin Homeostasis Hypothesis of Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Regulatory T (Treg) cells are a CD4 T-cell subset with an important role in immune tolerance; however, the mechanisms underlying Treg cell differentiation and function are incompletely understood. Here, we show that NFIL3/E4BP4, a transcription factor, plays a key role in Treg cell differentiation and function. Microarray analysis showed that Treg cells had lower Nfil3 expression than all other CD4 T-cell subsets. Overexpression of Nfil3 in Treg cells led to diminished expression of Foxp3 and other signature Treg genes, including Il2ra, Icos, Tnfrsf18, and Ctla4. Furthermore, Nfil3-overexpressing Treg cells exhibited impaired immunosuppressive activity in vitro and in vivo. We discovered that NFIL3 directly binds to and negatively regulates the expression of Foxp3. In addition, bisulfite sequencing revealed that NFIL3 induces methylation at Foxp3 locus regulatory CpG sites, which contributes to the control of Treg cell stability. Together, these data indicate that NFIL3 impairs Treg cell function through the downregulation of Foxp3 expression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.