PMID- 38011375
OWN - NLM
STAT- MEDLINE
DCOM- 20231221
LR  - 20240110
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 12
DP  - 2023 Nov 27
TI  - Regulation of pDC fate determination by histone deacetylase 3.
LID - 10.7554/eLife.80477 [doi]
LID - e80477
AB  - 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 Histone 
      deacetylase 3 (Hdac3), 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.
CI  - (c) 2023, Zhang, Wu, He et al.
FAU - Zhang, Yijun
AU  - Zhang Y
AD  - Institute for Immunology, Tsinghua-Peking Center for Life Sciences, School of 
      Medicine, Tsinghua University, Beijing, China.
AD  - Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing, 
      China.
FAU - Wu, Tao
AU  - Wu T
AUID- ORCID: 0000-0001-9347-5723
AD  - Institute for Immunology, Tsinghua-Peking Center for Life Sciences, School of 
      Medicine, Tsinghua University, Beijing, China.
AD  - Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing, 
      China.
FAU - He, Zhimin
AU  - He Z
AD  - Institute for Immunology, Tsinghua-Peking Center for Life Sciences, School of 
      Medicine, Tsinghua University, Beijing, China.
AD  - Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing, 
      China.
FAU - Lai, Wenlong
AU  - Lai W
AD  - Institute for Immunology, Tsinghua-Peking Center for Life Sciences, School of 
      Medicine, Tsinghua University, Beijing, China.
AD  - Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing, 
      China.
FAU - Shen, Xiangyi
AU  - Shen X
AUID- ORCID: 0000-0002-7460-1066
AD  - Institute for Immunology, Tsinghua-Peking Center for Life Sciences, School of 
      Medicine, Tsinghua University, Beijing, China.
AD  - Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing, 
      China.
FAU - Lv, Jiaoyan
AU  - Lv J
AD  - Institute for Immunology, Tsinghua-Peking Center for Life Sciences, School of 
      Medicine, Tsinghua University, Beijing, China.
AD  - Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing, 
      China.
FAU - Wang, Yuanhao
AU  - Wang Y
AD  - Institute for Immunology, Tsinghua-Peking Center for Life Sciences, School of 
      Medicine, Tsinghua University, Beijing, China.
AD  - Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing, 
      China.
FAU - Wu, Li
AU  - Wu L
AUID- ORCID: 0000-0002-2802-1220
AD  - Institute for Immunology, Tsinghua-Peking Center for Life Sciences, School of 
      Medicine, Tsinghua University, Beijing, China.
AD  - Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing, 
      China.
LA  - eng
SI  - GEO/GSE197212
SI  - GEO/GSE197207
GR  - National Key Research Project 2019YFA0508502/Ministry of Science and Technology 
      of the People's Republic of China/
GR  - 31991174/National Natural Science Foundation of China/
GR  - 31800769/National Natural Science Foundation of China/
GR  - National Key Research Project 2022YFC2505001/Ministry of Science and Technology 
      of the People's Republic of China/
PT  - Journal Article
DEP - 20231127
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - EC 3.5.1.98 (histone deacetylase 3)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
UOF - doi: 10.1101/2022.06.08.494949
MH  - Mice
MH  - Animals
MH  - *Gene Expression Regulation
MH  - *Histone Deacetylases/genetics/metabolism
MH  - Cell Differentiation/genetics
MH  - Dendritic Cells
PMC - PMC10732571
OTO - NOTNLM
OT  - H3K27ac
OT  - cell biology
OT  - histone deacetylase 3
OT  - immunology
OT  - inflammation
OT  - mouse
OT  - pDC development
COIS- YZ, TW, ZH, WL, XS, JL, YW, LW No competing interests declared
EDAT- 2023/11/27 18:43
MHDA- 2023/12/21 06:43
PMCR- 2023/11/27
CRDT- 2023/11/27 14:55
PHST- 2022/05/22 00:00 [received]
PHST- 2023/11/22 00:00 [accepted]
PHST- 2023/12/21 06:43 [medline]
PHST- 2023/11/27 18:43 [pubmed]
PHST- 2023/11/27 14:55 [entrez]
PHST- 2023/11/27 00:00 [pmc-release]
AID - 80477 [pii]
AID - 10.7554/eLife.80477 [doi]
PST - epublish
SO  - Elife. 2023 Nov 27;12:e80477. doi: 10.7554/eLife.80477.