TNFAIP3 Deficiency Affects Monocytes, Monocytes-Derived Cells and Microglia in Mice
Open Access
- 18 April 2020
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 21 (8), 2830
- https://doi.org/10.3390/ijms21082830
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.Funding Information
- Ministero della Salute (GR-2010-2315964)
- Fondazione Italiana Sclerosi Multipla (2010/R/7)
This publication has 30 references indexed in Scilit:
- Early Enriched Environment Exposure Protects Spatial Memory and Accelerates Amyloid Plaque Formation in APPSwe/PS1L166P MicePLOS ONE, 2013
- Unraveling Chemokine and Chemokine Receptor Expression Patterns Using Genetically Engineered MiceMethods in molecular biology (Clifton, N.J.), 2013
- A20: linking a complex regulator of ubiquitylation to immunity and human diseaseNature Reviews Immunology, 2012
- A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritisNature Genetics, 2011
- Return to homeostasis: downregulation of NF-κB responsesNature Immunology, 2011
- Rare variation at the TNFAIP3 locus and susceptibility to rheumatoid arthritisHuman Genetics, 2010
- Learning from Nature: Pregnancy Changes the Expression of Inflammation-Related Genes in Patients with Multiple SclerosisPLOS ONE, 2010
- The association of a nonsynonymous single‐nucleotide polymorphism in TNFAIP3 with systemic lupus erythematosus and rheumatoid arthritis in the Japanese populationArthritis & Rheumatism, 2010
- Overlapping genetic susceptibility variants between three autoimmune disorders: rheumatoid arthritis, type 1 diabetes and coeliac diseaseArthritis Research & Therapy, 2010
- Regulation of tissue homeostasis by NF-κB signalling: implications for inflammatory diseasesNature Reviews Immunology, 2009