Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple Sclerosis (MS) is a demyelinating/inflammatory disease of the central nervous system. Relapsing-remitting MS is characterized by a relapsing phase with clinical symptoms and the production of inflammatory cell infiltrates, and a period of remission during which patients recover partially. Myeloid-derived suppressor cells (MDSCs) are immature cells capable of suppressing the inflammatory response through Arginase-I (Arg-I) activity, among other mechanisms. Here, we have identified Arg-I(+) -MDSCs in the spinal cord during experimental autoimmune encephalomyelitis (EAE), cells that were largely restricted to the demyelinating plaque and that always exhibited the characteristic MDSC surface markers Arg-I/CD11b/Gr-1/M-CSF1R. The presence and density of Arg-I(+) -cells, and the proportion of apoptotic but not proliferative T cells, were correlated with the EAE time course: peaked in parallel with the clinical score, decreased significantly during the remitting phase and completely disappeared during the chronic phase. Spinal cord-isolated MDSCs of EAE animals augmented the cell death when co-cultured with stimulated control splenic CD3 T cells. These data point to an important role for MDSCs in limiting inflammatory damage in MS, favoring the relative recovery in the remitting phase of the disease. Thus, the MDSC population should be considered as a potential therapeutic target to accelerate the recovery of MS patients.
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PMID:Myeloid-derived suppressor cells limit the inflammation by promoting T lymphocyte apoptosis in the spinal cord of a murine model of multiple sclerosis. 2150 22

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by progressive neuronal demyelination and degeneration. Much of this damage can be attributed to microglia, the resident innate immune cells of the CNS, as well as monocyte-derived macrophages, which breach the blood-brain barrier in this inflammatory state. Upon activation, both microglia and macrophages release a variety of factors that greatly contribute to disease progression, and thus therapeutic approaches in MS focus on diminishing their activity. We use the CSF1R inhibitor PLX5622, administered in mouse chow, to ablate microglia and macrophages during the course of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Here, we show that ablation of these cells significantly improves animal mobility and weight gain in EAE. Further, we show that this treatment addresses the pathological hallmarks of MS, as it reduces demyelination and immune activation. White matter lesion areas in microglia/macrophage-depleted animals show substantial preservation of mature, myelinating oligodendrocytes in comparison to control animals. Taken together, these findings suggest that ablation of microglia/macrophages during the symptomatic phase of EAE reduces CNS inflammation and may also promote a more permissive environment for remyelination and recovery. This microglia and macrophage-targeted therapy could be a promising avenue for treatment of MS.
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PMID:Csf1R inhibition attenuates experimental autoimmune encephalomyelitis and promotes recovery. 2980 27

Cells of the adaptive and innate immune systems in the brain parenchyma and in the meningeal spaces contribute to physiologic functions and disease states in the central nervous system (CNS). Animal studies have demonstrated the involvement of immune constituents, along with major histocompatibility complex (MHC) molecules, in neural development and rare genetic disorders (e.g., colony stimulating factor 1 receptor [CSF1R] deficiency). Genome wide association studies suggest a comparable role of the immune system in humans. Although the CNS can be the target of primary autoimmune disorders, no current experimental model captures all of the features of the most common human disorder placed in this category, multiple sclerosis (MS). Such features include spontaneous onset, environmental contributions, and a recurrent/progressive disease course in a genetically predisposed host. Numerous therapeutic interventions related to antigen and cytokine specific therapies have demonstrated effectiveness in experimental autoimmune encephalomyelitis (EAE), the animal model used to define principles underlying immune-mediated mechanisms in MS. Despite the similarities in the two diseases, most treatments used to ameliorate EAE have failed to translate to the human disease. As directly demonstrated in animal models and implicated by correlative studies in humans, adaptive and innate immune constituents within the systemic compartment and resident in the CNS contribute to the disease course of neurodegenerative and neurobehavioral disorders. The expanding knowledge of the molecular properties of glial cells provides increasing insights into species related variables. These variables affect glial bidirectional interactions with the immune system as well as their own production of "immune molecules" that mediate tissue injury and repair.
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PMID:Species differences in immune-mediated CNS tissue injury and repair: A (neuro)inflammatory topic. 3172 70