ArticleGlia2019
Transcriptional regulation of homeostatic and disease-associated-microglial genes by IRF1, LXRβ, and CEBPα.
Article in Glia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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
43 citing papers in PubMed, 67 citations in OpenAlex.
- KOLF2.1J iTF-Microglia: A standardized platform to study microglial transcriptional regulatory networks in CNS disease.iScience · 2026Article
- Role of the miR-340-5p/IRF1/USP18 Axis in Neuroinflammation Associated with Epilepsy.Neurochemical research · 2026Article
- Integration of Transcriptional Signatures from Brain Tissue and Plasma Extracellular Vesicles of a Preclinical Tauopathy Mouse Model.International journal of molecular sciences · 2026Article
- Microglia‑mediated neuroinflammation in intracerebral hemorrhage: Pathological mechanisms and implications for therapeutic development (Review).International journal of molecular medicine · 2026Review
- Article
- A sex-biased response of the adult brain to Zika virus infection: from down-regulation of neuronal IRF3 to enhanced pathology in adult female mice.Cell communication and signaling : CCS · 2026Article
- Early microglial priming in Alzheimer's disease revealed by ME-seq.bioRxiv : the preprint server for biology · 2026Article
- Photoreceptor outer segments promote the accumulation of lipid droplets in microglia by reprogramming lipid metabolism.Frontiers in immunology · 2026Article
- The Immunopathogenesis of uveitis.Frontiers in medicine · 2026Review
- Neuroimmune Dysregulation and AI-Driven Therapeutic Strategies in Alzheimer's Disease.Cellular and molecular neurobiology · 2025Review
- Eupatilin ameliorates spinal cord injury by inhibiting damage-associated microglia and optimizing the regenerative microenvironment.iScience · 2025Article
- Inactivation of microglial LXRβ in early postnatal mice impairs microglia homeostasis and causes long-lasting cognitive dysfunction.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A factor-based analysis of individual human microglia uncovers regulators of an Alzheimer-related transcriptional signature.bioRxiv : the preprint server for biology · 2025Article
- Interferon Regulatory Factors as a Potential Therapeutic Target for Neuroinflammation: A Focus on Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Asrij/OCIAD1 depletion reduces inflammatory microglial activation and ameliorates Aβ pathology in an Alzheimer's disease mouse model.Journal of neuroinflammation · 2025Article
- Article
- Repeated LPS induces training and tolerance of microglial responses across brain regions.Journal of neuroinflammation · 2024Article
- Comparative gene regulatory networks modulatingmedRxiv : the preprint server for health sciences · 2024Article
- BHLHE40/41 regulate microglia and peripheral macrophage responses associated with Alzheimer's disease and other disorders of lipid-rich tissues.Nature communications · 2024Article
- The Impact of Dipyridamole on Disease-Associated Microglia Phenotypic Transformation in White Matter Lesions Induced by Chronic Cerebral Hypoperfusion.Neurochemical research · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Microglia transform from homeostatic to disease-associated-microglia (DAM) profiles in neurodegeneration. Within DAM, we recently identified distinct pro-inflammatory and anti-inflammatory sub-profiles although transcriptional regulators of homeostatic and distinct DAM profiles remain unclear. Informed by these studies, we nominated CEBPα, IRF1, and LXRβ as likely regulators of homeostatic, pro-inflammatory and anti-inflammatory DAM states and performed in-vitro siRNA studies in primary microglia to identify roles of each transcriptional factor (TF) in regulating microglial activation, using an integrated transcriptomics, bioinformatics and experimental validation approach. Efficient (>70%) silencing of TFs in microglia revealed reciprocal regulation between each TF specifically following pro-inflammatory activation. Neuroinflammatory transcriptomic profiling of microglia coupled with qPCR validation revealed distinct gene clusters with unique patterns of regulation by each TF, which were independent of LPS stimulation. While all three TFs (especially IRF1 and LXRβ) positively regulated core DAM genes (Apoe, Axl, Clec7a, Tyrobp, and Trem2) as well as homeostatic and pro-inflammatory DAM genes, LPS, and IFNγ increased pro-inflammatory DAM but suppressed homeostatic and anti-inflammatory DAM gene expression via an Erk1/2-dependent signaling pathway. IRF1 and LXRβ silencing suppressed microglial phagocytic activity for polystyrene microspheres as well as fAβ42 while IRF1 silencing strongly suppressed production of pro-inflammatory cytokines in response to LPS. Our studies reveal complex transcriptional regulation of homeostatic and DAM profiles whereby IRF1, LXRβ, and CEBPα positively regulate both pro- and anti-inflammatory DAM genes while activating stimuli independently augment pro-inflammatory DAM responses and suppress homeostatic and anti-inflammatory responses via Erk signaling. This framework can guide development of therapeutic immuno-modulatory strategies for neurodegeneration.
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.