RRC ID 58404
Author Montarolo F, Perga S, Tessarolo C, Spadaro M, Martire S, Bertolotto A.
Title TNFAIP3 Deficiency Affects Monocytes, Monocytes-Derived Cells and Microglia in Mice.
Journal Int J Mol Sci
Abstract 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-naïve 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.
Volume 21(8)
Published 2020-4-18
DOI 10.3390/ijms21082830
PII ijms21082830
PMID 32325694
PMC PMC7215837
MeSH Animals Body Weight / genetics Bone Marrow Cells / cytology Bone Marrow Cells / immunology Central Nervous System / cytology Central Nervous System / metabolism Female Flow Cytometry Granulocyte Precursor Cells / cytology Granulocyte Precursor Cells / metabolism Inflammation / immunology Lymph Nodes / cytology Lymph Nodes / immunology Macrophages / cytology Macrophages / immunology Male Mice Mice, Knockout Microglia / cytology* Microglia / metabolism Monocytes / cytology* Monocytes / immunology Monocytes / metabolism Myeloid Cells / cytology Myeloid Cells / immunology Myeloid Cells / metabolism Myelopoiesis / genetics* Spleen / cytology Spleen / immunology Tumor Necrosis Factor alpha-Induced Protein 3 / deficiency* Tumor Necrosis Factor alpha-Induced Protein 3 / genetics Tumor Necrosis Factor alpha-Induced Protein 3 / metabolism
IF 4.556
Times Cited 0
Mice RBRC05494