Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
De, Sá, Fernandes, C; Novoszel, P; Gastaldi, T; Krauß, D; Lang, M; Rica, R; Kutschat, AP; Holcmann, M; Ellmeier, W; Seruggia, D; Strobl, H; Sibilia, M.
The histone deacetylase HDAC1 controls dendritic cell development and anti-tumor immunity.
Cell Rep. 2024; 43(6):114308
Doi: 10.1016/j.celrep.2024.114308
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Lang Magdalena
- Strobl Herbert
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- Abstract:
- Dendritic cell (DC) progenitors adapt their transcriptional program during development, generating different subsets. How chromatin modifications modulate these processes is unclear. Here, we investigate the impact of histone deacetylation on DCs by genetically deleting histone deacetylase 1 (HDAC1) or HDAC2 in hematopoietic progenitors and CD11c-expressing cells. While HDAC2 is not critical for DC development, HDAC1 deletion impairs pro-pDC and mature pDC generation and affects ESAM+cDC2 differentiation from tDCs and pre-cDC2s, whereas cDC1s are unchanged. HDAC1 knockdown in human hematopoietic cells also impairs cDC2 development, highlighting its crucial role across species. Multi-omics analyses reveal that HDAC1 controls expression, chromatin accessibility, and histone acetylation of the transcription factors IRF4, IRF8, and SPIB required for efficient development of cDC2 subsets. Without HDAC1, DCs switch immunologically, enhancing tumor surveillance through increased cDC1 maturation and interleukin-12 production, driving T helper 1-mediated immunity and CD8+ T cell recruitment. Our study reveals the importance of histone acetylation in DC development and anti-tumor immunity, suggesting DC-targeted therapeutic strategies for immuno-oncology.
- Find related publications in this database (using NLM MeSH Indexing)
- Dendritic Cells - metabolism, immunology
- Histone Deacetylase 1 - metabolism
- Animals - administration & dosage
- Humans - administration & dosage
- Cell Differentiation - administration & dosage
- Mice - administration & dosage
- Mice, Inbred C57BL - administration & dosage
- Acetylation - administration & dosage
- Neoplasms - immunology, pathology
- Histones - metabolism
- CD8-Positive T-Lymphocytes - immunology, metabolism
- Histone Deacetylase 2 - metabolism
- Interleukin-12 - metabolism