PMID- 34903641
OWN - NLM
STAT- MEDLINE
DCOM- 20220201
LR  - 20240210
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 208
IP  - 2
DP  - 2022 Jan 15
TI  - DNMT1 Deficiency Impacts on Plasmacytoid Dendritic Cells in Homeostasis and 
      Autoimmune Disease.
PG  - 358-370
LID - 10.4049/jimmunol.2100624 [doi]
AB  - Dendritic cells (DCs) are heterogeneous immune regulators involved in autoimmune 
      diseases. Epigenomic mechanisms orchestrating DC development and DC subset 
      diversification remain insufficiently understood but could be important to 
      modulate DC fate for clinical purposes. By combining whole-genome methylation 
      assessment with the analysis of mice expressing reduced DNA methyltransferase 1 
      levels, we show that distinct DNA methylation levels and patterns are required 
      for the development of plasmacytoid DC and conventional DC subsets. We provide 
      clonal in vivo evidence for DC lineage establishment at the stem cell level, and 
      we show that a high DNA methylation threshold level is essential for 
      Flt3-dependent survival of DC precursors. Importantly, reducing methylation 
      predominantly depletes plasmacytoid DC and alleviates systemic lupus 
      erythematosus in an autoimmunity mouse model. This study shows how DNA 
      methylation regulates the production of DC subsets and provides a potential 
      rationale for targeting autoimmune disease using hypomethylating agents.
CI  - Copyright (c) 2022 by The American Association of Immunologists, Inc.
FAU - Czeh, Melinda
AU  - Czeh M
AD  - Institute of Molecular Tumor Biology, University of Munster, Munster, Germany.
AD  - MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, 
      John Radcliffe Hospital, University of Oxford, Oxford, UK.
FAU - Stable, Sina
AU  - Stable S
AUID- ORCID: 0000-0002-5962-2440
AD  - Section Translational Cancer Epigenomics, Division of Translational Medical 
      Oncology, German Cancer Research Center and National Center for Tumor Diseases 
      Heidelberg, Heidelberg, Germany.
FAU - Kramer, Stephen
AU  - Kramer S
AD  - Section Translational Cancer Epigenomics, Division of Translational Medical 
      Oncology, German Cancer Research Center and National Center for Tumor Diseases 
      Heidelberg, Heidelberg, Germany.
AD  - Biomedical Informatics, Data Mining and Data Analytics, Faculty of Applied 
      Computer Science and Medical Faculty, University of Augsburg, Germany.
AD  - Bioinformatics and Omics Data Analysis, German Cancer Research Center, 
      Heidelberg, Germany.
AD  - Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.
FAU - Tepe, Lena
AU  - Tepe L
AD  - Institute of Molecular Tumor Biology, University of Munster, Munster, Germany.
FAU - Talyan, Sweta
AU  - Talyan S
AUID- ORCID: 0000-0002-7160-6742
AD  - Faculty of Biology, Johannes Gutenberg University of Mainz, Mainz, Germany.
FAU - Carrelha, Joana
AU  - Carrelha J
AD  - MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, 
      John Radcliffe Hospital, University of Oxford, Oxford, UK.
FAU - Meng, Yiran
AU  - Meng Y
AUID- ORCID: 0000-0002-9333-2383
AD  - MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, 
      John Radcliffe Hospital, University of Oxford, Oxford, UK.
FAU - Heitplatz, Barbara
AU  - Heitplatz B
AD  - Gerhard-Domagk-Institute of Pathology, University Hospital Munster, University of 
      Munster, Munster, Germany.
FAU - Schwabenland, Marius
AU  - Schwabenland M
AUID- ORCID: 0000-0003-2205-5427
AD  - Institute of Neuropathology, Faculty of Medicine, University of Freiburg, 
      Freiburg, Germany.
FAU - Milsom, Michael D
AU  - Milsom MD
AUID- ORCID: 0000-0002-3567-254X
AD  - Division of Experimental Hematology, German Cancer Research Center, Heidelberg, 
      Germany.
FAU - Plass, Christoph
AU  - Plass C
AUID- ORCID: 0000-0003-2554-3952
AD  - Division of Cancer Epigenomics, German Cancer Research Center, Heidelberg, 
      Germany.
FAU - Prinz, Marco
AU  - Prinz M
AD  - Institute of Neuropathology, Faculty of Medicine, University of Freiburg, 
      Freiburg, Germany.
AD  - Centre for Biological Signalling Studies and Centre for Integrative Biological 
      Signalling Studies, University of Freiburg, Freiburg, Germany.
AD  - Center for Basics in NeuroModulation, Faculty of Medicine, University of 
      Freiburg, Freiburg, Germany.
FAU - Schlesner, Matthias
AU  - Schlesner M
AUID- ORCID: 0000-0002-5896-4086
AD  - Biomedical Informatics, Data Mining and Data Analytics, Faculty of Applied 
      Computer Science and Medical Faculty, University of Augsburg, Germany.
AD  - Bioinformatics and Omics Data Analysis, German Cancer Research Center, 
      Heidelberg, Germany.
FAU - Andrade-Navarro, Miguel A
AU  - Andrade-Navarro MA
AUID- ORCID: 0000-0001-6650-1711
AD  - Faculty of Biology, Johannes Gutenberg University of Mainz, Mainz, Germany.
FAU - Nerlov, Claus
AU  - Nerlov C
AD  - MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, 
      John Radcliffe Hospital, University of Oxford, Oxford, UK.
FAU - Jacobsen, Sten Eirik W
AU  - Jacobsen SEW
AD  - MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, 
      John Radcliffe Hospital, University of Oxford, Oxford, UK.
AD  - Department of Cell and Molecular Biology and Department of Medicine Huddinge, 
      Center for Hematology and Regenerative Medicine, Karolinska Institutet, 
      Stockholm, Sweden; and.
AD  - Karolinska University Hospital, Stockholm, Sweden.
FAU - Lipka, Daniel B
AU  - Lipka DB
AUID- ORCID: 0000-0001-5081-7869
AD  - Section Translational Cancer Epigenomics, Division of Translational Medical 
      Oncology, German Cancer Research Center and National Center for Tumor Diseases 
      Heidelberg, Heidelberg, Germany.
FAU - Rosenbauer, Frank
AU  - Rosenbauer F
AUID- ORCID: 0000-0001-7977-9421
AD  - Institute of Molecular Tumor Biology, University of Munster, Munster, Germany; 
      frank.rosenbauer@ukmuenster.de.
LA  - eng
GR  - MC_UU_00016/7/MRC_/Medical Research Council/United Kingdom
GR  - MC_UU_12009/5/MRC_/Medical Research Council/United Kingdom
GR  - A24872/CRUK_/Cancer Research UK/United Kingdom
GR  - 24872/CRUK_/Cancer Research UK/United Kingdom
GR  - G0501838/MRC_/Medical Research Council/United Kingdom
GR  - MC_UU_00029/9/MRC_/Medical Research Council/United Kingdom
GR  - MC_UU_00016/5/MRC_/Medical Research Council/United Kingdom
GR  - G0801073/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211213
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1)
RN  - EC 2.1.1.37 (Dnmt1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Autoimmunity/genetics
MH  - Bone Marrow Cells/immunology
MH  - Cell Differentiation/immunology
MH  - DNA (Cytosine-5-)-Methyltransferase 1/*genetics/*metabolism
MH  - DNA Methylation/*genetics
MH  - Dendritic Cells/cytology/*immunology
MH  - Gene Expression Profiling
MH  - Hematopoietic Stem Cells/cytology
MH  - Homeostasis/*immunology
MH  - Lupus Erythematosus, Systemic/*immunology
MH  - Mice
MH  - Mice, Knockout
PMC - PMC7612220
MID - EMS138142
COIS- Disclosure of Conflicts of Interest The authors declare that they have no 
      conflict of interest.
EDAT- 2021/12/15 06:00
MHDA- 2022/02/02 06:00
PMCR- 2022/07/15
CRDT- 2021/12/14 06:50
PHST- 2021/06/25 00:00 [received]
PHST- 2021/10/28 00:00 [accepted]
PHST- 2021/12/15 06:00 [pubmed]
PHST- 2022/02/02 06:00 [medline]
PHST- 2021/12/14 06:50 [entrez]
PHST- 2022/07/15 00:00 [pmc-release]
AID - jimmunol.2100624 [pii]
AID - 10.4049/jimmunol.2100624 [doi]
PST - ppublish
SO  - J Immunol. 2022 Jan 15;208(2):358-370. doi: 10.4049/jimmunol.2100624. Epub 2021 
      Dec 13.