Search results for "LOM"
showing 10 items of 4424 documents
Thymus-derived regulatory T cells are positively selected on natural self-antigen through cognate interactions of high functional avidity
2016
Regulatory T (Treg) cells expressing Foxp3 transcripton factor are essential for immune homeostasis. They arise in the thymus as a separate lineage from conventional CD4+Foxp3- T (Tconv) cells. Here, we show that the thymic development of Treg cells depends on the expression of their endogenous cognate self-antigen. The formation of these cells was impaired in mice lacking this self-antigen, while Tconv cell development was not negatively affected. Thymus-derived Treg cells were selected by self-antigens in a specific manner, while autoreactive Tconv cells were produced through degenerate recognition of distinct antigens. These distinct modes of development were associated with the expressi…
IL-17 controls central nervous system autoimmunity through the intestinal microbiome
2021
Interleukin-17A- (IL-17A) and IL-17F-producing CD4(+) T helper cells (T(H)17 cells) are implicated in the development of chronic inflammatory diseases, such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). T-H 17 cells also orchestrate leukocyte invasion of the central nervous system (CNS) and subsequent tissue damage. However, the role of IL-17A and IL-17F as effector cytokines is still confused with the encephalitogenic function of the cells that produce these cytokines, namely, T-H 17 cells, fueling a long-standing debate in the neuroimmunology field. Here, we demonstrated that mice deficient for IL-17A/F lose their susceptibility to EAE, which…
CNS-localized myeloid cells capture living invading T cells during neuroinflammation
2020
Using an in vivo real-time approach, the authors show that local myeloid cells remove early CNS-invading T cells via an engulfment pathway that is dependent on N-acetyl-D-glucosamine (GlcNAc) and lectin. These results reveal a novel capacity of myeloid cells to counteract neuroinflammation.
Targeting Voltage-Dependent Calcium Channels with Pregabalin Exerts a Direct Neuroprotective Effect in an Animal Model of Multiple Sclerosis
2018
Background/aims Multiple sclerosis (MS) is a prototypical autoimmune central nervous system (CNS) disease. Particularly progressive forms of MS (PMS) show significant neuroaxonal damage as consequence of demyelination and neuronal hyperexcitation. Immuno-modulatory treatment strategies are beneficial in relapsing MS (RMS), but mostly fail in PMS. Pregabalin (Lyrica®) is prescribed to MS patients to treat neuropathic pain. Mechanistically, it targets voltage-dependent Ca2+ channels and reduces harmful neuronal hyperexcitation in mouse epilepsy models. Studies suggest that GABA analogues like pregabalin exert neuroprotective effects in animal models of ischemia and trauma. Methods We tested t…
A Drosophila model of GDAP1 function reveals the involvement of insulin signalling in the mitochondria-dependent neuromuscular degeneration
2017
[EN] Charcot-Marie-Tooth disease is a rare peripheral neuropathy for which there is no specific treatment. Some forms of Charcot-Marie-Tooth are due to mutations in the GDAP1 gene. A striking feature of mutations in GDAP1 is that they have a variable clinical manifestation, according to disease onset and progression, histology and mode of inheritance. Studies in cellular and animal models have revealed a role of GDAP1 in mitochondrial morphology and distribution, calcium homeostasis and oxidative stress. To get a better understanding of the disease mechanism we have generated models of over-expression and RNA interference of the Drosophila Gdapl gene. In order to get an overview about the c…
Single-cell profiling reveals GPCR heterogeneity and functional patterning during neuroinflammation.
2017
GPCR expression was intensively studied in bulk cDNA of leukocyte populations, but limited data are available with respect to expression in individual cells. Here, we show a microfluidic-based single-cell GPCR expression analysis in primary T cells, myeloid cells, and endothelial cells under naive conditions and during experimental autoimmune encephalomyelitis, the mouse model of multiple sclerosis. We found that neuroinflammation induces characteristic changes in GPCR heterogeneity and patterning, and we identify various functionally relevant subgroups with specific GPCR profiles among spinal cord-infiltrating CD4 T cells, macrophages, microglia, or endothelial cells. Using GPCRs CXCR4, S1…
A rare association of chronic lymphocytic leukemia with c-ANCA-positive Wegener’s granulomatosis: a case report
2016
Background Wegener’s granulomatosis is a systemic vasculitis of the small- and medium-sized vessels, produced by the action of ANCA, which involves the respiratory tract, kidneys, and eyes, with a potential for lethal evolution in the first year after diagnosis. Its association with chronic lymphocytic leukemia is rarely described in the literature, and it may be difficult to diagnose and to treat this association. Case presentation We present the case of a 73-year-old Caucasian patient, a rare case in which Wegener’s granulomatosis is associated in a patient with chronic lymphocytic leukemia, who is admitted in the Infectious Disease Department for fever, diplopia, headache, purulent and h…
[Au(9-methylcaffein-8-ylidene) 2 ] + /DNA Tel23 System: Solution, Computational, and Biological Studies
2017
International audience; Physicochemical methods have been used to investigate interactions occurring in solution between the dicarbene gold(I) complex [Au(9‐methylcaffein‐8‐ylidene)2]BF4 (AuNHC) and a human telomeric DNA sequence, namely Tel23. Circular dichroism measurements allow identification of the conformational changes experienced by Tel23 upon interaction with AuNHC, and the respective binding stoichiometries and constants were determined. Computational studies provide a good link between previous crystallographic results of the same system and the present solution data, offering an exhaustive description of the inherent noncovalent metallodrug–DNA interactions. Remarkably, we found…
Enhanced autophagic-lysosomal activity and increased BAG3-mediated selective macroautophagy as adaptive response of neuronal cells to chronic oxidati…
2019
Oxidative stress and a disturbed cellular protein homeostasis (proteostasis) belong to the most important hallmarks of aging and of neurodegenerative disorders. The proteasomal and autophagic-lysosomal degradation pathways are key measures to maintain proteostasis. Here, we report that hippocampal cells selected for full adaptation and resistance to oxidative stress induced by hydrogen peroxide (oxidative stress-resistant cells, OxSR cells) showed a massive increase in the expression of components of the cellular autophagic-lysosomal network and a significantly higher overall autophagic activity. A comparative expression analysis revealed that distinct key regulators of autophagy are upregu…
Proteomics and Metabolomics Studies and Clinical Outcomes
2018
Abstract The application of proteomics and metabolomics to the field of human reproduction arose as a result of the need to identify new diagnostic and therapeutic tools that improve fertilization, implantation, and live birth rates in assisted reproduction cycles. A better understanding of the molecular mechanisms underlying the physiology of germ cells, embryos, and the endometrium has been made possible through the identification of their proteomic and metabolomic profiles. This has led to the discovery of specific biomarkers for the diagnosis, treatment, and counseling of several infertility-related conditions and for a more objective selection of the best gametes and embryos and the mo…