ArticleNature communications2025
Histone lactylation promotes rheumatoid arthritis progression by increasing NFATc2 expression and the production of anti-lactylated histone autoantibodies.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Resetting immunometabolic set points in autoimmune disease.Journal of translational autoimmunity · 2026Review
- Protein acylation and bone metabolism: bidirectional crosstalk linking metabolic reprogramming to skeletal homeostasis.Journal of molecular histology · 2026Review
- Immunomodulatory metabolites in rheumatic diseases.EULAR rheumatology open · 2026Review
- Single-cell and spatial transcriptomics reveal lactate-active epithelial-immune cell crosstalk that reprograms the immune microenvironment in colorectal cancer.Translational oncology · 2026Article
- Lactate metabolism and protein lactylation in inflammatory and tumor microenvironments.Molecular biomedicine · 2026Review
- The emerging role of lactate in skeletal homeostasis and disorders: Integrated mechanisms and translational opportunities.Journal of orthopaedic translation · 2026Review
- Review
- Role of LDHA in senescent fibroblast exosomes promoting ferroptosis via histone lactylation-mediated ACSL4 regulation in skin photoaging.Epigenetics & chromatin · 2026Article
- Lactate programs CRIP1 protein lactylation to drive synovial proliferation in rheumatoid arthritis.JCI insight · 2026Article
- Inhibiting lactylation for efficient treatment of renal fibrosis through targeting nanomedicine of renal lactate accumulation in obstructed kidney.Journal of nanobiotechnology · 2026Article
- Immunometabolic reprogramming in rheumatoid arthritis: the epitranscriptomic role of N6-methyladenosine in innate and adaptive immunity.Frontiers in immunology · 2026Review
- Injectable Hyaluronic Acid-Functionalized Nanocomposite Hydrogel for Targeted Rheumatoid Arthritis Therapy via Concurrent ROS Attenuation and Macrophage Repolarization.International journal of nanomedicine · 2026Article
- Immunological heterogeneity in rheumatoid arthritis: challenges in early-stage stratification, non-response to targeted therapy, and the restoration of immune tolerance.Frontiers in immunology · 2026Review
- Dynamic Balance of Histone H3 Methylation: Regulatory Mechanisms and Therapeutic Prospects in RA Immune Dysregulation and Bone Metabolism Imbalance.Journal of immunology research · 2026Review
- A novel role of the TNF-α/p65/IRF1 axis in aggravating rheumatoid arthritis through the induction of fibroblast-like synoviocytes pyroptosis.Frontiers in pharmacology · 2026Article
- Identification of Immune-Related Lactylation Genes in Rheumatoid Arthritis With Atherosclerosis: A Comprehensive Analysis Using Bulk and Single-Cell RNA Sequencing Data.Mediators of inflammation · 2026Article
- Lactate-driven lactylation reprograms chondrocyte fate and joint inflammation in osteoarthritis: linking metabolism with epigenetic regulation.Frontiers in cell and developmental biology · 2026Review
- Stimuli-Responsive Nanoplatforms for Precision Intervention in Rheumatoid Arthritis.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnologyReview
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Authors and funding
13 authors.
Funding
Abstract
Elevated lactate in the joint microenvironment of rheumatoid arthritis patients is crucial for disease progression, though the mechanism remains unclear. This study shows significantly increased global lactylation levels within fibroblast-like synoviocytes from RA patients compared to healthy controls, with lactylated proteins being enriched in histones. Furthermore, we find anti-lactylated histone autoantibodies present in RA patients that positively correlate with Disease Activity Score 28. Using CUT&Tag and RNA-seq, we identify NFATc2 as a key target gene regulated by histone H3 lysine 9 lactylation. Functional studies reveal that NFATc2 promotes migration of RA-FLSs. Additionally, using collagen antibody-induced arthritis and collagen-induced arthritis mouse models, we demonstrate that NFATc2 exacerbates RA disease progression through enhancing the cartilage invasive function of FLS. Here, we show that upregulated target gene NFATc2 by lactate-dependent histone lactylation, can be used as a potential therapeutic target for intervention, anti-lactylated histone autoantibodies is promising as a diagnostic marker for RA.
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