Publications by authors named "Norbert Minet"
De novo synthesis of the pyrimidine, cytidine triphosphate (CTP), is crucial for DNA/RNA metabolism and depends on the CTP synthetases, CTPS1 and -2. Partial CTPS1 deficiency in humans has previously been shown to lead to immunodeficiency, with impaired expansion of T and B cells. Here, we examine the effects of conditional and inducible inactivation of Ctps1 and/or Ctps2 on mouse embryonic development and immunity.
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- The study investigates the use of mucosal-associated invariant T (MAIT) cells to prevent or reduce graft-versus-host disease (GVHD), a significant complication after stem cell transplants.
- Researchers found that MAIT cells can inhibit the activation of alloreactive T cells in vitro and effectively delay or lessen the severity of GVHD in a preclinical mouse model when given shortly after PBMC infusion.
- The immunosuppressive effects of MAIT cells were linked to reduced levels of inflammatory cytokines like IFN-γ and TNF-α, while increasing anti-inflammatory IL-10, suggesting MAIT cells could be a promising treatment for GVHD and related conditions in future
Differential roles of CTP synthetases CTPS1 and CTPS2 in cell proliferation.
Life Sci Alliance
September 2023
The CTP nucleotide is a key precursor of nucleic acids metabolism essential for DNA replication. De novo CTP production relies on CTP synthetases 1 and 2 (CTPS1 and CTPS2) that catalyze the conversion of UTP into CTP. CTP synthetase activity is high in proliferating cells including cancer cells; however, the respective roles of CTPS1 and CTPS2 in cell proliferation are not known.
View Article and Find Full Text PDFLymphoma is the most common hematological malignancy and is among the 10 most prevalent cancers worldwide. Although survival has been improved by modern immunochemotherapeutic regimens, there remains a significant need for novel targeted agents to treat both B-cell and T-cell malignancies. Cytidine triphosphate synthase 1 (CTPS1), which catalyzes the rate-limiting step in pyrimidine synthesis, plays an essential and nonredundant role in B-cell and T-cell proliferation but is complemented by the homologous CTPS2 isoform outside the hemopoietic system.
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- CTPS1 deficiency results from a specific gene mutation that leads to severe immune issues, making patients more vulnerable to bacterial and viral infections.
- Immune profiling of affected patients revealed low levels of certain immune cells, particularly mucosal-associated T cells and memory B cells, while other immune cell types were normal.
- The CTPS1 mutant protein exhibited significantly reduced activity, and its instability is linked to impaired T cell proliferation, suggesting CTPS1 could be a potential target for treatments aimed at managing T cell-related diseases.
Cytidine 5'-triphosphate synthetase (CTPS) is known to be a central enzyme in the de novo synthesis of CTP. We have recently demonstrated that a deficiency in CTPS1 is associated with an impaired capacity of activated lymphocytes to proliferate leading to a combined immunodeficiency disease. In order to better document its role in immunomodulation, we developed a method for measuring CTPS activity in human lymphocytes.
View Article and Find Full Text PDFNetrins are secreted molecules involved in axon guidance and angiogenesis. We previously showed that Netrin-4 acts as an anti-angiogenic factor by inhibiting endothelial cell (EC) functions. In this study, we investigated the effects of Netrin-4 on vascular smooth muscle cell (VSMC) activity in vitro and in vivo.
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