ArticleScience immunology2021
Cutaneous innate immune tolerance is mediated by epigenetic control of MAP2K3 by HDAC8/9.
Article in Science immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Histone and Histone Acetylation-Related Alterations of Gene Expression in Uninvolved Psoriatic Skin and Their Effects on Cell Proliferation, Differentiation, and Immune Responses.International journal of molecular sciences · 2023Pooled it
- The transcription elongation factors Spt4 and Spt6 promote dermal adipocyte differentiation.Adipocyte · 2026Article
- Acne: epidemiology, risk factors, pathogenesis, management and cutting-edge research.Signal transduction and targeted therapy · 2026Review
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Ubiquitin-like proteins NEDD8 and SUMO2 control epithelial homeostasis, regeneration, and inflammation.Science (New York, N.Y.) · 2026Article
- Proteomic and experimental analyses reveal molecular signatures of flexural atopic dermatitis in antecubital and popliteal fossae and the therapeutic effect of Aida lotion.Frontiers in immunology · 2026Article
- The multifactorial role of HDAC9 at the maternal-fetal interface in the pathogenesis of preeclampsia.Clinical science (London, England : 1979) · 2025Review
- Localization and quantification of placentalPhysiological genomics · 2025Article
- Review
- Comprehensive genome analysis and variant detection at scale using DRAGEN.Nature biotechnology · 2025Article
- IFN-α and vitamin B6-induced galectin-9 promotes the immunomodulatory function of human clonal mesenchymal stem cells.Stem cell research & therapy · 2025Article
- Maternal asthma imprints fetal lung ILC2s via glucocorticoid signaling leading to worsened allergic airway inflammation in murine adult offspring.Nature communications · 2025Article
- Histones deacetylases in the epidermis: structure, functions and therapeutic implications.Frontiers in epigenetics and epigenomics · 2025Review
- Exploring the influence of gut microbiota metabolites on vitiligo through the gut-skin axis.Frontiers in microbiology · 2025Review
- The Central Roles of Keratinocytes in Coordinating Skin Immunity.The Journal of investigative dermatology · 2024Review
- Article
- The Switch/Sucrose Nonfermentable Subunit ARID1A Mediates Neutrophil-Associated Skin Inflammatory Responses.The Journal of investigative dermatology · 2024Article
- Discovery of a Highly Potent and Selective HDAC8 Degrader: Advancing the Functional Understanding and Therapeutic Potential of HDAC8.Journal of medicinal chemistry · 2024Article
- Short-chain fatty acids: linking diet, the microbiome and immunity.Nature reviews. Immunology · 2024Review
- Genomic Regions Associated with Resistance to Gastrointestinal Nematode Parasites in Sheep-A Review.Genes · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The skin typically tolerates exposure to various microbes and chemicals in the environment. Here, we investigated how the epidermis maintains this innate immune tolerance to stimuli that are recognized by Toll-like receptors (TLRs). Loss of tolerance to TLR ligands occurred after silencing of the histone deacetylases (HDACs) HDAC8 and HDAC9 in keratinocytes. Transcriptional analysis identified MAP2K3 as suppressed by HDAC8/9 activity and a potential key intermediary for establishing this tolerance. HDAC8/9 influenced acetylation at H3K9 and H3K27 marks in the MAP2K3 promoter. Proteomic analysis further identified SSRP1 and SUPT16H as associated with HDAC8/9 and responsible for transcriptional elongation of MAP2K3. Silencing of MAP2K3 blocked the capacity of HDAC8/9 to influence cytokine responses. Relevance in vivo was supported by observations of increased MAP2K3 in human inflammatory skin conditions and the capacity of keratinocyte HDAC8/9 to influence dendritic cell maturation and T cell proliferation. Keratinocyte-specific deletion of HDAC8/9 also increased inflammation in mice after exposure to ultraviolet radiation, imiquimod, or
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.