ArticleNature communications2025
Keratinocyte-specific H4K12 lactylation drives a non-canonical IL-17-dependent signaling in psoriasis progression in mice.
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 14 papers.
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Who cites it
14 citing papers in PubMed.
- Lactate metabolism and protein lactylation in inflammatory and tumor microenvironments.Molecular biomedicine · 2026Review
- Matrix Metalloproteinase-9 (MMP-9) in Psoriasis: Integrating Extracellular Matrix Remodeling, Neutrophil-Endothelial Crosstalk and Biomarker Evidence.Medical sciences (Basel, Switzerland) · 2026Review
- The crosstalk between RNA m6A modification and protein lactylation: emerging insights into tumor progression.Oncogene · 2026Review
- AARS1-catalyzed H4K12 lactylation promotes HCC resistance to targeted therapy by activating RAPGEF3-RAP1 signaling.Cell death & disease · 2026Article
- Protein lactylation in cancer: principles, programmes and therapeutic opportunities.Molecular cancer · 2026Review
- Creatine metabolism regulates trophectoderm formation in early mouse embryos via an energy-cytoskeleton-YAP axis.The Journal of biological chemistry · 2026Article
- A Novel Approach to Neuropathic Pain Treatment: Lactylation Targeting Microglia.Molecular neurobiology · 2026Review
- Development of perilla essential oil-based nanoemulsions as anti-psoriatic and dermal delivery platforms for topical therapy.International journal of pharmaceutics: X · 2026Article
- Identification and Screening of Lactate-Related Genes as Molecular Markers for Early Diagnosis of Steroid-Induced Osteonecrosis of the Femoral Head.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Role of the STAT3 Signaling Pathway in Cell Proliferation and Inflammation in Psoriasis and Approaches for Targeted Therapies: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Machine learning meets psoriasis: identifying key lactylation biomarkers as potential targets for diagnosis and therapies.Frontiers in immunology · 2026Article
- The active immune role of keratinocytes: from passive targets to key hubs in psoriatic inflammation.Frontiers in immunology · 2026Review
- Targeting the PCSK9-PR-IL-17 axis for psoriasis therapy.Frontiers in pharmacology · 2026Article
- The role of protein lactylation in skin diseases: from molecular mechanisms to potential therapeutics.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
IL-17 signaling contributes to the pathogenesis of psoriasis; however, IL-17 involvement in keratinocyte hyperactivation of epidermis remains unclear. Here, we describe an IL-17A-induced, skin-specific, positive feedback loop, which operates independently of canonical chemokine production, thus untangling skin inflammation and epithelial hyperproliferation in psoriasis. We show that IL-17A-induced, keratinocyte-specific KLK8 interacts with IL-17R to promote histone H4 lysine lactylation (H4K12la) catalyzed by the acetyltransferase HAT1. H4K12la further promotes IL-17A-mediated keratinocyte proliferation and the expression of KLK8 and IL-17R, creating a feedback loop that drives psoriasis progression. Importantly, excessive lactate in the microenvironment exacerbates H4K12la and psoriasis severity, thereby impairing the efficacy of anti-IL-17A antibody. Silencing KLK8, HAT1, or inhibiting lactate accumulation attenuates psoriasis in mice. Moreover, combining lactylation inhibition with anti-IL-17A therapy exhibits synergistic effects against antibody-resistant psoriasis. Thus, our findings unveil a lactylation-driven, keratinocyte-specific IL-17A signaling and offer a promising approach for psoriasis treatment, particularly in patients with comorbid metabolic syndrome.
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