Inhibiting LSD1 unlocks retinoid AP-1 programming to activate epithelial immunity and skin tumor suppression - PubMed
7 hours ago
- #Epigenetics
- #Immunology
- #Cancer
- LSD1 (Lysine-specific demethylase 1) acts as a brake on retinoid- and AP-1-driven enhancer activation in the epidermis.
- Inhibition of LSD1 in adult skin triggers pathways related to retinoic acid signaling, lipid remodeling, and chemokine induction.
- LSD1 occupies enhancer regions with AP-1 motifs, and its loss increases H3K4me1/2, activating a poised AP-1-retinoid program.
- Keratinocyte subsets initiate retinoid signaling to recruit dendritic cells and activate CD4+ T cell responses upon LSD1 inhibition.
- Topical LSD1 inhibition suppresses cutaneous squamous cell carcinoma and enhances keratinocyte-immune crosstalk.
- CD4+ T cells are essential for tumor control, while retinoid signaling partially contributes to the anti-tumor effects.
- LSD1 is identified as a master repressor of epithelial immune competence, suggesting its inhibition as a therapeutic strategy for skin cancer.