Regulation of pDC fate determination by histone deacetylase 3

• Published in: eLife Vol. 12
• Main Authors: Zhang, Yijun, Wu, Tao, He, Zhimin, Lai, Wenlong, Shen, Xiangyi, Lv, Jiaoyan, Wang, Yuanhao, Wu, Li
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 27-11-2023; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Acetylation; Animals; Antigen-presenting cells; Antigens; Bone marrow; Cell Biology; Cell culture; Cell Differentiation - genetics; Dendritic Cells; Developmental stages; Epigenetic inheritance; Epigenetics; Flow cytometry; FLT3L protein; Gene Expression Regulation; Gene regulation; Genes; H3K27ac; Hemopoiesis; Histone deacetylase; histone deacetylase 3; Histone Deacetylases - genetics; Histone Deacetylases - metabolism; Homeostasis; Immune response; Immunology and Inflammation; Mice; pDC development; Progenitor cells; Spleen; Stem cells; Transcription factors; mouse; cell biology; inflammation; H3K27ac; histone deacetylase 3; pDC development; immunology
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.80477

Dendritic cells (DCs), the key antigen-presenting cells, are primary regulators of immune responses. Transcriptional regulation of DC development had been one of the major research interests in DC biology; however, the epigenetic regulatory mechanisms during DC development remains unclear. Here, we report that
(
), an important epigenetic regulator, is highly expressed in pDCs, and its deficiency profoundly impaired the development of pDCs. Significant disturbance of homeostasis of hematopoietic progenitors was also observed in HDAC3-deficient mice, manifested by altered cell numbers of these progenitors and defective differentiation potentials for pDCs. Using the in vitro Flt3L supplemented DC culture system, we further demonstrated that HDAC3 was required for the differentiation of pDCs from progenitors at all developmental stages. Mechanistically, HDAC3 deficiency resulted in enhanced expression of cDC1-associated genes, owing to markedly elevated H3K27 acetylation (H3K27ac) at these gene sites in BM pDCs. In contrast, the expression of pDC-associated genes was significantly downregulated, leading to defective pDC differentiation.