PMID- 32325694
OWN - NLM
STAT- MEDLINE
DCOM- 20210202
LR  - 20210202
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 8
DP  - 2020 Apr 18
TI  - TNFAIP3 Deficiency Affects Monocytes, Monocytes-Derived Cells and Microglia in 
      Mice.
LID - 10.3390/ijms21082830 [doi]
LID - 2830
AB  - The intracellular-ubiquitin-ending-enzyme tumor necrosis factor alpha-induced 
      protein 3 (TNFAIP3) is a potent inhibitor of the pro-inflammatory nuclear factor 
      kappa-light-chain-enhancer of activated B cell (NF-kB) pathway. Single nucleotide 
      polymorphisms in TNFAIP3 locus have been associated to autoimmune inflammatory 
      disorders, including Multiple Sclerosis (MS). Previously, we reported a TNFAIP3 
      down-regulated gene expression level in blood and specifically in monocytes 
      obtained from treatment-naive MS patients compared to healthy controls (HC). 
      Myeloid cells exert a key role in the pathogenesis of MS. Here we evaluated the 
      effect of specific TNFAIP3 deficiency in myeloid cells including monocytes, 
      monocyte-derived cells (M-MDC) and microglia analyzing lymphoid organs and 
      microglia of mice. TNFAIP3 deletion is induced using conditional knock-out mice 
      for myeloid lineage. Flow-cytometry and histological procedures were applied to 
      assess the immune cell populations of spleen, lymph nodes and bone marrow and 
      microglial cell density in the central nervous system (CNS), respectively. We 
      found that TNFAIP3 deletion in myeloid cells induces a reduction in body weight, 
      a decrease in the number of M-MDC and of common monocyte and granulocyte 
      precursor cells (CMGPs). We also reported that the lack of TNFAIP3 in myeloid 
      cells induces an increase in microglial cell density. The results suggest that 
      TNFAIP3 in myeloid cells critically controls the development of M-MDC in lymphoid 
      organ and of microglia in the CNS.
FAU - Montarolo, Francesca
AU  - Montarolo F
AUID- ORCID: 0000-0002-3633-8746
AD  - Neuroscience Institute Cavalieri Ottolenghi (NICO), Orbassano, 10043 Turin, 
      Italy.
AD  - Neurobiology Unit, Neurology-CReSM (Regional Referring Center of Multiple 
      Sclerosis), AOU San Luigi Gonzaga, Orbassano, 10043 Turin, Italy.
AD  - Department of Molecular Biotechnology and Health Sciences, University of Turin, 
      10126 Turin, Italy.
FAU - Perga, Simona
AU  - Perga S
AD  - Neuroscience Institute Cavalieri Ottolenghi (NICO), Orbassano, 10043 Turin, 
      Italy.
AD  - Neurobiology Unit, Neurology-CReSM (Regional Referring Center of Multiple 
      Sclerosis), AOU San Luigi Gonzaga, Orbassano, 10043 Turin, Italy.
AD  - Department of Neuroscience "Rita Levi Montalcini", University of Turin, 10125 
      Turin, Italy.
FAU - Tessarolo, Carlotta
AU  - Tessarolo C
AD  - Neuroscience Institute Cavalieri Ottolenghi (NICO), Orbassano, 10043 Turin, 
      Italy.
AD  - Neurobiology Unit, Neurology-CReSM (Regional Referring Center of Multiple 
      Sclerosis), AOU San Luigi Gonzaga, Orbassano, 10043 Turin, Italy.
FAU - Spadaro, Michela
AU  - Spadaro M
AD  - Neuroscience Institute Cavalieri Ottolenghi (NICO), Orbassano, 10043 Turin, 
      Italy.
AD  - Neurobiology Unit, Neurology-CReSM (Regional Referring Center of Multiple 
      Sclerosis), AOU San Luigi Gonzaga, Orbassano, 10043 Turin, Italy.
FAU - Martire, Serena
AU  - Martire S
AD  - Neuroscience Institute Cavalieri Ottolenghi (NICO), Orbassano, 10043 Turin, 
      Italy.
AD  - Neurobiology Unit, Neurology-CReSM (Regional Referring Center of Multiple 
      Sclerosis), AOU San Luigi Gonzaga, Orbassano, 10043 Turin, Italy.
FAU - Bertolotto, Antonio
AU  - Bertolotto A
AUID- ORCID: 0000-0002-7052-1907
AD  - Neuroscience Institute Cavalieri Ottolenghi (NICO), Orbassano, 10043 Turin, 
      Italy.
AD  - Neurobiology Unit, Neurology-CReSM (Regional Referring Center of Multiple 
      Sclerosis), AOU San Luigi Gonzaga, Orbassano, 10043 Turin, Italy.
LA  - eng
GR  - GR-2010-2315964/Ministero della Salute/
GR  - 2010/R/7/Fondazione Italiana Sclerosi Multipla/
PT  - Journal Article
DEP - 20200418
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - EC 3.4.19.12 (Tumor Necrosis Factor alpha-Induced Protein 3)
RN  - EC 3.4.22.- (Tnfaip3 protein, mouse)
SB  - IM
MH  - Animals
MH  - Body Weight/genetics
MH  - Bone Marrow Cells/cytology/immunology
MH  - Central Nervous System/cytology/metabolism
MH  - Female
MH  - Flow Cytometry
MH  - Granulocyte Precursor Cells/cytology/metabolism
MH  - Inflammation/immunology
MH  - Lymph Nodes/cytology/immunology
MH  - Macrophages/cytology/immunology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Microglia/*cytology/metabolism
MH  - Monocytes/*cytology/immunology/metabolism
MH  - Myeloid Cells/cytology/immunology/metabolism
MH  - Myelopoiesis/*genetics
MH  - Spleen/cytology/immunology
MH  - Tumor Necrosis Factor alpha-Induced Protein 3/*deficiency/genetics/metabolism
PMC - PMC7215837
OTO - NOTNLM
OT  - TNFAIP3
OT  - inflammation
OT  - microglia
OT  - monocyte and macrophage
OT  - myeloid cells
COIS- The authors declare no conflicts of interest.
EDAT- 2020/04/25 06:00
MHDA- 2021/02/03 06:00
PMCR- 2020/04/01
CRDT- 2020/04/25 06:00
PHST- 2020/03/13 00:00 [received]
PHST- 2020/04/07 00:00 [revised]
PHST- 2020/04/15 00:00 [accepted]
PHST- 2020/04/25 06:00 [entrez]
PHST- 2020/04/25 06:00 [pubmed]
PHST- 2021/02/03 06:00 [medline]
PHST- 2020/04/01 00:00 [pmc-release]
AID - ijms21082830 [pii]
AID - ijms-21-02830 [pii]
AID - 10.3390/ijms21082830 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Apr 18;21(8):2830. doi: 10.3390/ijms21082830.