Experimental autoimmune encephalomyelitis
About: Experimental autoimmune encephalomyelitis is a research topic. Over the lifetime, 9154 publications have been published within this topic receiving 467680 citations.
Papers published on a yearly basis
TL;DR: Mucosally derived TH2-like clones induced by oral antigen can actively regulate immune responses in vivo and may represent a different subset of T cells.
Abstract: Experimental autoimmune encephalomyelitis (EAE) is a cell-mediated autoimmune disease that serves as an animal model for multiple sclerosis. Oral administration of myelin basic protein (MBP) suppresses EAE by inducing peripheral tolerance. T cell clones were isolated from the mesenteric lymph nodes of SJL mice that had been orally tolerized to MBP. These clones were CD4+ and were structurally identical to T helper cell type 1 (TH1) encephalitogenic CD4+ clones in T cell receptor usage, major histocompatibility complex restriction, and epitope recognition. However, they produced transforming growth factor-beta with various amounts of interleukin-4 and interleukin-10 and suppressed EAE induced with either MBP or proteolipid protein. Thus, mucosally derived TH2-like clones induced by oral antigen can actively regulate immune responses in vivo and may represent a different subset of T cells.
TL;DR: MCC950 treatment rescued neonatal lethality in a mouse model of CAPS and was active in ex vivo samples from individuals with Muckle–Wells syndrome, and is a potential therapeutic for NLRP3-associated syndromes, and a tool for further study of theNLRP3 inflammasome in human health and disease.
Abstract: The NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome is a component of the inflammatory process, and its aberrant activation is pathogenic in inherited disorders such as cryopyrin-associated periodic syndrome (CAPS) and complex diseases such as multiple sclerosis, type 2 diabetes, Alzheimer's disease and atherosclerosis. We describe the development of MCC950, a potent, selective, small-molecule inhibitor of NLRP3. MCC950 blocked canonical and noncanonical NLRP3 activation at nanomolar concentrations. MCC950 specifically inhibited activation of NLRP3 but not the AIM2, NLRC4 or NLRP1 inflammasomes. MCC950 reduced interleukin-1β (IL-1β) production in vivo and attenuated the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis. Furthermore, MCC950 treatment rescued neonatal lethality in a mouse model of CAPS and was active in ex vivo samples from individuals with Muckle-Wells syndrome. MCC950 is thus a potential therapeutic for NLRP3-associated syndromes, including autoinflammatory and autoimmune diseases, and a tool for further study of the NLRP3 inflammasome in human health and disease.
TL;DR: In vitro adhesion assay on tissue sections found that lymphocytes and monocytes bound selectively to inflamed EAE brain vessels, and therapies designed to interfere with α4βl integrin may be useful in treating inflammatory diseases of the central nervous system, such as multiple sclerosis.
Abstract: Experimental autoimmune encephalomyelitis (EAE) is an inflammatory condition of the central nervous system with similarities to multiple sclerosis In both diseases, circulating leukocytes penetrate the blood-brain barrier and damage myelin, resulting in impaired nerve conduction and paralysis We sought to identify the adhesion receptors that mediate the attachment of circulating leukocytes to inflamed brain endothelium in EAE, because this interaction is the first step in leukocyte entry into the central nervous system Using an in vitro adhesion assay on tissue sections, we found that lymphocytes and monocytes bound selectively to inflamed EAE brain vessels Binding was inhibited by antibodies against the integrin molecule alpha 4 beta 1, but not by antibodies against numerous other adhesion receptors When tested in vivo, anti-alpha 4 integrin effectively prevented the accumulation of leukocytes in the central nervous system and the development of EAE Thus, therapies designed to interfere with alpha 4 beta 1 integrin may be useful in treating inflammatory diseases of the central nervous system, such as multiple sclerosis
TL;DR: Large-scale analysis of transcripts in MS lesions elucidates new aspects of pathology and opens possibilities for therapy, and results in EAE corroborate the microarray studies on MS lesions.
Abstract: Microarray analysis of multiple sclerosis (MS) lesions obtained at autopsy revealed increased transcripts of genes encoding inflammatory cytokines, particularly interleukin-6 and -17, interferon-gamma and associated downstream pathways. Comparison of two poles of MS pathology--acute lesions with inflammation versus 'silent' lesions without inflammation--revealed differentially transcribed genes. Some products of these genes were chosen as targets for therapy of experimental autoimmune encephalomyelitis (EAE) in mice. Granulocyte colony-stimulating factor is upregulated in acute, but not in chronic, MS lesions, and the effect on ameliorating EAE is more pronounced in the acute phase, in contrast to knocking out the immunoglobulin Fc receptor common gamma chain where the effect is greatest on chronic disease. These results in EAE corroborate the microarray studies on MS lesions. Large-scale analysis of transcripts in MS lesions elucidates new aspects of pathology and opens possibilities for therapy.
TL;DR: The identification of the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) as a regulator of Treg and TH17 cell differentiation in mice is reported, constituting a unique target for therapeutic immunomodulation.
Abstract: Regulatory T cells (Treg) expressing the transcription factor Foxp3 control the autoreactive components of the immune system. The development of Treg cells is reciprocally related to that of pro-inflammatory T cells producing interleukin-17 (TH17). Although Treg cell dysfunction and/or TH17 cell dysregulation are thought to contribute to the development of autoimmune disorders, little is known about the physiological pathways that control the generation of these cell lineages. Here we report the identification of the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) as a regulator of Treg and TH17 cell differentiation in mice. AHR activation by its ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin induced functional Treg cells that suppressed experimental autoimmune encephalomyelitis. On the other hand, AHR activation by 6-formylindolo[3,2-b]carbazole interfered with Treg cell development, boosted TH17 cell differentiation and increased the severity of experimental autoimmune encephalomyelitis in mice. Thus, AHR regulates both Treg and TH17 cell differentiation in a ligand-specific fashion, constituting a unique target for therapeutic immunomodulation. The aryl hydrocarbon receptor (AHR) is a transcription factor best known for mediating the toxicity of aromatic hydrocarbons such as dioxin: its activation leads to the production of detoxification enzymes. AHR has been intensely studied in relation to toxicology and cancer research, but no mechanistic connection to the immune system was known. Now two groups report a role for AHR in maintaining the balance between two T-lymphocyte populations — the Treg and TH17 cells — that are part of the immune regulation system dealing with tolerance of self-antigens and pathogen clearance. Both groups also show that AHR affects the severity of experimental autoimmune encephalitis, a mouse model of multiple sclerosis. This work raises the possibility that stimulation of AHR by environmental factors could be involved in the development of autoimmune disease, and point to AHR as a possible drug target for immunomodulation. The aryl hydrocarbon receptor (AHR) is the cellular receptor for a number of environment contaminants. It is shown here to induce regulatory T cells when bound to the ligand TCCD and promote TH17 differentiation when bound to FICZ.
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