PMID- 38316548
OWN - NLM
STAT- MEDLINE
DCOM- 20240403
LR  - 20240409
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Linking)
VI  - 172
IP  - 1
DP  - 2024 May
TI  - Chromatin-binding deubiquitinase MYSM1 acts in haematopoietic progenitors to 
      control dendritic cell development and to program dendritic cell responses to 
      microbial stimulation.
PG  - 109-126
LID - 10.1111/imm.13758 [doi]
AB  - Dendritic cells (DCs) are the most significant antigen presenting cells of the 
      immune system, critical for the activation of naive T cells. The pathways 
      controlling DC development, maturation, and effector function therefore require 
      precise regulation to allow for an effective induction of adaptive immune 
      response. MYSM1 is a chromatin binding deubiquitinase (DUB) and an activator of 
      gene expression via its catalytic activity for monoubiquitinated histone H2A 
      (H2A-K119ub), which is a highly abundant repressive epigenetic mark. MYSM1 is an 
      important regulator of haematopoiesis in mouse and human, and a systemic 
      constitutive loss of Mysm1 in mice results in a depletion of many haematopoietic 
      progenitors, including DC precursors, with the downstream loss of most DC lineage 
      cells. However, the roles of MYSM1 at the later checkpoints in DC development, 
      maturation, activation, and effector function at present remain unknown. In the 
      current work, using a range of novel mouse models (Mysm1(fl)Cre(ERT2), 
      Mysm1(fl)CD11c-cre, Mysm1(DN)), we further the understanding of MYSM1 functions 
      in the DC lineage: assessing the requirement for MYSM1 in DC development 
      independently of other complex developmental phenotypes, exploring its role at 
      the later checkpoints in DC maintenance and activation in response to microbial 
      stimulation, and testing the requirement for the DUB catalytic activity of MYSM1 
      in these processes. Surprisingly, we demonstrate that MYSM1 expression and 
      catalytic activity in DCs are dispensable for the maintenance of DC numbers in 
      vivo or for DC activation in response to microbial stimulation. In contrast, 
      MYSM1 acts via its DUB catalytic activity specifically in haematopoietic 
      progenitors to allow normal DC lineage development, and its loss results not only 
      in a severe DC depletion but also in the production of functionally altered DCs, 
      with a dysregulation of many housekeeping transcriptional programs and 
      significantly altered responses to microbial stimulation.
CI  - (c) 2024 The Authors. Immunology published by John Wiley & Sons Ltd.
FAU - Mousa, Marwah
AU  - Mousa M
AD  - Department of Physiology, McGill University, Montreal, Quebec, Canada.
AD  - McGill University Research Centre on Complex Traits, McGill University, Montreal, 
      Quebec, Canada.
FAU - Liang, Yue
AU  - Liang Y
AD  - Department of Physiology, McGill University, Montreal, Quebec, Canada.
AD  - McGill University Research Centre on Complex Traits, McGill University, Montreal, 
      Quebec, Canada.
FAU - Tung, Lin Tze
AU  - Tung LT
AD  - Department of Physiology, McGill University, Montreal, Quebec, Canada.
AD  - McGill University Research Centre on Complex Traits, McGill University, Montreal, 
      Quebec, Canada.
FAU - Wang, HanChen
AU  - Wang H
AD  - Department of Physiology, McGill University, Montreal, Quebec, Canada.
AD  - McGill University Research Centre on Complex Traits, McGill University, Montreal, 
      Quebec, Canada.
FAU - Krawczyk, Connie
AU  - Krawczyk C
AUID- ORCID: 0000-0002-2468-5986
AD  - Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand 
      Rapids, Michigan, United States.
FAU - Langlais, David
AU  - Langlais D
AD  - McGill University Research Centre on Complex Traits, McGill University, Montreal, 
      Quebec, Canada.
AD  - Department of Human Genetics, McGill University Genome Centre, McGill University, 
      Montreal, Quebec, Canada.
AD  - Department of Microbiology and Immunology, McGill University, Montreal, Quebec, 
      Canada.
FAU - Nijnik, Anastasia
AU  - Nijnik A
AUID- ORCID: 0000-0001-6048-4631
AD  - Department of Physiology, McGill University, Montreal, Quebec, Canada.
AD  - McGill University Research Centre on Complex Traits, McGill University, Montreal, 
      Quebec, Canada.
LA  - eng
GR  - CAPMC/CIHR/Canada
GR  - CAPMC/CIHR/Canada
PT  - Journal Article
DEP - 20240205
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Chromatin)
RN  - EC 3.4.- (Endopeptidases)
RN  - 0 (Histones)
RN  - 0 (MYSM1 protein, human)
RN  - 0 (Trans-Activators)
RN  - EC 3.4.19.12 (Ubiquitin-Specific Proteases)
RN  - EC 3.4.19.12 (MYSM1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - Cell Differentiation
MH  - Chromatin/genetics
MH  - Dendritic Cells/metabolism
MH  - Endopeptidases/genetics/metabolism
MH  - Histones/metabolism
MH  - Mice, Knockout
MH  - *Trans-Activators/genetics/metabolism
MH  - *Ubiquitin-Specific Proteases/genetics/metabolism
OTO - NOTNLM
OT  - cell differentiation
OT  - dendritic cells
OT  - flow cytometry
OT  - gene regulation
OT  - transgenic/knockout mice
EDAT- 2024/02/06 00:42
MHDA- 2024/04/03 06:45
CRDT- 2024/02/05 21:37
PHST- 2023/07/23 00:00 [received]
PHST- 2024/01/08 00:00 [accepted]
PHST- 2024/04/03 06:45 [medline]
PHST- 2024/02/06 00:42 [pubmed]
PHST- 2024/02/05 21:37 [entrez]
AID - 10.1111/imm.13758 [doi]
PST - ppublish
SO  - Immunology. 2024 May;172(1):109-126. doi: 10.1111/imm.13758. Epub 2024 Feb 5.