SIRT1 inactivation switches reactive astrocytes to an antiinflammatory phenotype in CNS autoimmunity.

Astrocytes are highly heterogeneous in their phenotype and function, which contributes to CNS disease, repair, and aging; however, the molecular mechanism of their functional states remains largely unknown. Here, we show that activation of sirtuin 1 (SIRT1), a protein deacetylase, played an important role in the detrimental actions of reactive astrocytes, whereas its inactivation conferred these cells with antiinflammatory functions that inhibited the production of proinflammatory mediators by myeloid cells and microglia and promoted the differentiation of oligodendrocyte progenitor cells. Mice with astrocyte-specific Sirt1 knockout (Sirt1-/-) had suppressed progression of experimental autoimmune encephalomyelitis (EAE), an animal model of CNS inflammatory demyelinating disease.

The SNX-482 peptide from Hysterocrates gigas spider acts as an immunomodulatory molecule activating macrophages.

Peptides are molecules that have emerged as crucial candidates for the development of anticancer drugs. Spider venoms are a rich source of peptides (venom peptides - VPs) with biological effects. VPs have been tested as adjuvants in the activation of cells of the immune system with the aim of improving immunotherapies for the treatment of neoplasms.

IFN-β Acts on Monocytes to Ameliorate CNS Autoimmunity by Inhibiting Proinflammatory Cross-Talk Between Monocytes and Th Cells.

IFN-β has been the treatment for multiple sclerosis (MS) for almost three decades, but understanding the mechanisms underlying its beneficial effects remains incomplete. We have shown that MS patients have increased numbers of GM-CSF Th cells in circulation, and that IFN-β therapy reduces their numbers. GM-CSF expression by myelin-specific Th cells is essential for the development of experimental autoimmune encephalomyelitis (EAE), an animal model of MS.

Can tetracyclines ensure help in multiple sclerosis immunotherapy?

Background: Multiple sclerosis (MS) is a disease of the central nervous system where an autoimmune response leads to chronic inflammation. It represents the second leading cause of non-traumatic disability in the world, affecting mainly young adults and with high female to male incidence. At present, the causative agent in MS is unknown, preventing the development of prophylaxis policies and the understanding of how the human system copes with this complex inflammation.

Components from spider venom activate macrophages against glioblastoma cells: new potential adjuvants for anticancer immunotherapy.

Immunomodulation has been considered an important approach in the treatment of malignant tumours. However, the modulation of innate immune cells remains an underexplored tool. Studies from our group demonstrated that the Phoneutria nigriventer spider venom (PnV) administration increased the infiltration of macrophage in glioblastoma, in addition to decreasing the tumour size in a preclinical model.

Interferon-γ/Interleukin-27 Axis Induces Programmed Death Ligand 1 Expression in Monocyte-Derived Dendritic Cells and Restores Immune Tolerance in Central Nervous System Autoimmunity.

Antigen (Ag)-specific tolerance induction by intravenous (i. v.) injection of high-dose auto-Ags has been explored for therapy of autoimmune diseases, including multiple sclerosis (MS).

Oligodendrocyte-derived extracellular vesicles as antigen-specific therapy for autoimmune neuroinflammation in mice.

Autoimmune diseases such as multiple sclerosis (MS) develop because of failed peripheral immune tolerance for a specific self-antigen (Ag). Numerous approaches for Ag-specific suppression of autoimmune neuroinflammation have been proven effective in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. One such approach is intravenous tolerance induction by injecting a myelin Ag used for triggering EAE.

Matrine Inhibits CNS Autoimmunity Through an IFN-β-Dependent Mechanism.

Matrine (MAT), a quinolizidine alkaloid component derived from the root of , suppresses experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), by inducing the production of immunomodulatory molecules, e.g., IL-10.

Paracoccidioides brasiliensis infection increases regulatory T cell counts in female C57BL/6 mice infected via two distinct routes.

Studies that show an overview of the peripheral immune response in a model of Paracoccidioides brasiliensis (Pb) infection in females are scarce in the literature. We sought to characterize the innate and adaptive immune responses in female C57BL/6 mice infected with Pb through two distinct routes of administration, intranasal and intravenous. In addition to the lung, P.

Primaquine elicits Foxp3 regulatory T cells with a superior ability to limit CNS autoimmune inflammation.

Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) are neuroinflammatory conditions where inflammatory CD4 T cells play a major role. Forkhead box P3 (Foxp3) regulatory T (Treg) cells suppress inflammation and an increase in their numbers and activity is beneficial for MS and EAE. However, studies have shown that Treg cells can transdifferentiate to pathogenic Th17 cells under inflammatory conditions.

Comprehensive Analysis of the Immune and Stromal Compartments of the CNS in EAE Mice Reveal Pathways by Which Chloroquine Suppresses Neuroinflammation.

Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) are neuroinflammatory diseases of the central nervous system (CNS), where leukocytes and CNS resident cells play important roles in disease development and pathogenesis. The antimalarial drug chloroquine (CQ) has been shown to suppress EAE by modulating dendritic cells (DCs) and Th17 cells. However, the mechanism of action by which CQ modulates EAE is far from being elucidated.

Dimethyl fumarate suppresses granulocyte macrophage colony-stimulating factor-producing Th1 cells in CNS neuroinflammation.

Objective: To study the immunomodulatory effect of dimethyl fumarate (DF) on granulocyte macrophage colony-stimulating factor (GM-CSF) production in CD4 T cells in experimental autoimmune encephalomyelitis (EAE) and human peripheral blood mononuclear cells (PBMCs).

Methods: We collected splenocytes and CD4 T cells from C57BL/6 wild-type and interferon (IFN)-γ-deficient mice. For human PBMCs, venous blood was collected from healthy donors, and PBMCs were collected using the Percoll gradient method.

Spider venom administration impairs glioblastoma growth and modulates immune response in a non-clinical model.

Molecules from animal venoms are promising candidates for the development of new drugs. Previous in vitro studies have shown that the venom of the spider Phoneutria nigriventer (PnV) is a potential source of antineoplastic components with activity in glioblastoma (GB) cell lines. In the present work, the effects of PnV on tumor development were established in vivo using a xenogeneic model.

IL-9 Controls Central Nervous System Autoimmunity by Suppressing GM-CSF Production.

Multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) are inflammatory diseases of the CNS in which Th17 cells play a major role in the disease pathogenesis. Th17 cells that secrete GM-CSF are pathogenic and drive inflammation of the CNS. IL-9 is a cytokine with pleiotropic functions, and it has been suggested that it controls the pathogenic inflammation mediated by Th17 cells, and IL-9R mice develop more severe EAE compared with wild-type counterparts.

Immunomodulatory and neuroprotective mechanisms of Huangqi glycoprotein treatment in experimental autoimmune encephalomyelitis.

Previous studies have shown that Huangqi glycoprotein (HQGP) has an anti-inflammatory effect in vitro, and suppressed experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis; however, the mechanism underlying its effect is largely unknown. In this manuscript we investigated the mechanisms by which HQGP protect mice from EAE. HQGP was extracted from Astragalus membranaceus and purified by anion-exchange and gel filtration chromatography.

Mdivi-1, a mitochondrial fission inhibitor, modulates T helper cells and suppresses the development of experimental autoimmune encephalomyelitis.

Background: Unrestrained activation of Th1 and Th17 cells is associated with the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). While inactivation of dynamin-related protein 1 (Drp1), a GTPase that regulates mitochondrial fission, can reduce EAE severity by protecting myelin from demyelination, its effect on immune responses in EAE has not yet been studied.

Methods: We investigated the effect of Mdivi-1, a small molecule inhibitor of Drp1, on EAE.

Roles of GM-CSF in the Pathogenesis of Autoimmune Diseases: An Update.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was first described as a growth factor that induces the differentiation and proliferation of myeloid progenitors in the bone marrow. GM-CSF also has an important cytokine effect in chronic inflammatory diseases by stimulating the activation and migration of myeloid cells to inflammation sites, promoting survival of target cells and stimulating the renewal of effector granulocytes and macrophages. Because of these pro-cellular effects, an imbalance in GM-CSF production/signaling may lead to harmful inflammatory conditions.

Hypoglycemic, hypolipidemic and antioxidant effects of iridoid glycosides extracted from : possible involvement of the PI3K-Akt/PKB signaling pathway.

Iridoid glycosides (CIG) are the major component of . In this work, we researched the antioxidative, hypoglycemic and lowering blood lipids effects of CIG on diabetic mice induced by a high-fat diet (HFD) and streptozotocin (STZ). Furthermore, to investigate the molecular mechanism of action, the phosphorylation and protein expression of phosphoinositide 3-kinase (PI3K) and its downstream proteins, such as insulin receptor (INSR), protein kinase B (Akt/PKB) and glucose transporter 4 (GLUT4) have been detected.

The impact of metabolic reprogramming on dendritic cell function.

Dendritic cells (DCs) are antigen-presenting cells with the ability to activate naïve T cells and direct the adaptive cellular immune response toward a specific profile. This is important, as different pathogens demand specific "profiles" of immune responses for their elimination. Such a goal is achieved depending on the maturation/activation status of DCs by the time of antigen presentation to T cells.

Chloroquine-treated dendritic cells require STAT1 signaling for their tolerogenic activity.

MS and EAE are T cell-driven autoimmune diseases of the CNS where IL-17-producing Th17 cells promote damage and are pathogenic. Conversely, tolerogenic DCs induce Treg cells and suppress Th17 cells. Chloroquine (CQ) suppresses EAE through the modulation of DCs by unknown mechanisms.