ArticleJCI insight2019
Myeloid Folliculin balances mTOR activation to maintain innate immunity homeostasis.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- FLCN loss is characterized by SQSTM1/p62 accumulation despite functional autophagy flux in Birt-Hogg-Dubé syndrome-associated kidney cancer.Autophagy reports · 2026Article
- A novel uORF regulates folliculin to promote cell growth and lysosomal biogenesis during cardiac stress.Scientific reports · 2025Article
- mTORC1, the maestro of cell metabolism and growth.Genes & development · 2025Review
- The Spectrum of Renal "TFEopathies": Flipping the mTOR Switch in Renal Tumorigenesis.Physiology (Bethesda, Md.) · 2024Review
- Ragopathies and the rising influence of RagGTPases on human diseases.Nature communications · 2024Review
- Early-life exercise induces immunometabolic epigenetic modification enhancing anti-inflammatory immunity in middle-aged male mice.Nature communications · 2024Article
- Article
- A lysosomal regulatory circuit essential for the development and function of microglia.Science advances · 2022Article
- Inhibition of nonalcoholic fatty liver disease in mice by selective inhibition of mTORC1.Science (New York, N.Y.) · 2022Article
- Folliculin promotes substrate-selective mTORC1 activity by activating RagC to recruit TFE3.PLoS biology · 2022Article
- Loss of hepatic Flcn protects against fibrosis and inflammation by activating autophagy pathways.Scientific reports · 2021Article
- NRF-1 directly regulates TFE3 and promotes the proliferation of renal cancer cells.Oncology letters · 2021Article
- MiT Family Transcriptional Factors in Immune Cell Functions.Molecules and cells · 2021Review
- Folliculin: A Regulator of Transcription Through AMPK and mTOR Signaling Pathways.Frontiers in cell and developmental biology · 2021Review
- A FLCN-TFE3 Feedback Loop Prevents Excessive Glycogenesis and Phagocyte Activation by Regulating Lysosome Activity.Cell reports · 2020Article
- Key Roles of MiT Transcription Factors in Innate Immunity and Inflammation.Trends in immunology · 2020Review
- MiT/TFE Family of Transcription Factors: An Evolutionary Perspective.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The mTOR pathway is central to most cells. How mTOR is activated in macrophages and modulates macrophage physiology remain poorly understood. The tumor suppressor Folliculin (FLCN) is a GAP for RagC/D, a regulator of mTOR. We show here that LPS potently suppresses FLCN in macrophages, allowing nuclear translocation of the transcription factor TFE3, leading to lysosome biogenesis, cytokine production, and hypersensitivity to inflammatory signals. Nuclear TFE3 additionally activates a transcriptional RagD positive feedback loop that stimulates FLCN-independent canonical mTOR signaling to S6K and increases cellular proliferation. LPS thus simultaneously suppresses the TFE3 arm and activates the S6K arm of mTOR. In vivo, mice lacking myeloid FLCN reveal chronic macrophage activation, leading to profound histiocytic infiltration and tissue disruption, with hallmarks of human histiocytic syndromes like Erdheim-Chester Disease. Our data thus identify a critical FLCN-mTOR-TFE3 axis in myeloid cells, modulated by LPS, that balances mTOR activation and curbs innate immune responses.
Indexed as
Identifiers
What OpenQuestion holds
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.