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)

Experimental allergic encephalomyelitis (EAE) can be transferred by spleen cells stimulated in vitro with D-mannose-binding lectins but not with N-acetyl-D-galactosamine (GalNAc)-binding lectins. EAE could also be passively transferred by spleen cells following incubation with wheat germ agglutinin (WGA), in which case the disease transfer was abolished by the specific hapten inhibitor, N-acetyl-D-glucosamine. In the presence of rat T cell monoclonal antibody, either W3/25 or OX-8, both concanavalin A and Wisteria floribunda agglutinin stimulated helper and suppressor T subpopulations. On the other hand, GalNAc-binding lectins were less effective than D-mannose-binding lectins in generating interleukin 2 (IL2) in the culture supernatant, whereas WGA-stimulated spleen cells did not produce IL2. Furthermore, spleen cells cultured with pure IL2 could not transfer EAE to the recipients. These data suggest that some factors distinct from IL2 are required for the differentiation of EAE-effector precursors into the final effector cells in this transfer system.
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PMID:Adoptive transfer of experimental allergic encephalomyelitis with lectin-activated spleen cells. Part 2. Studies on T cell subsets and interleukin 2 production. 348 46

Multiple sclerosis (MS) is characterized with multifocal demyelination resulting from activation and infiltration of inflammatory cells into the central nerve system. Recent reports suggest that p38 mitogen-activated protein kinase (MAPK) / serum- and glucocorticoid-inducible protein kinase 1 (SGK1) signaling pathway contributes to the pathology of MS through regulation of immunity. However, the role of this signaling pathway in MS-related macrophage activation and polarization has not been studied. Here, we used an experimental autoimmune encephalomyelitis (EAE) model for MS to study the role of p38MAPK/SGK1 signaling in the macrophage polarization and its effects on the development and severity of EAE. Here, we found that p38MAPK/SGK1 signaling is required for IL4-induced M2 macrophage polarization in vitro. Chitin-induced M2 macrophage polarization reduces the severity of EAE in mice. Generation of an adeno-associated virus (AAV) carrying sh-p38 or sh-SGK1 under the control of a CD68 promoter successfully knockdown p38 or SGK1 levels in vitro and in vivo. Treatment with AAV-sh-p38 or AAV-sh-SGK1 abolished the effects of Chitin on macrophage polarization and the severity of EAE. Thus, our data suggest that p38MAPK/SGK1 signaling induces M2 macrophage polarization, which reduces the severity of EAE, a model for MS.
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PMID:p38MAPK/SGK1 signaling regulates macrophage polarization in experimental autoimmune encephalomyelitis. 3071 17

To study the role of myeloid cells in the central nervous system (CNS) in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), we used intravital microscopy, assessing local cellular interactions in vivo in EAE animals and ex vivo in organotypic hippocampal slice cultures. We discovered that myeloid cells actively engulf invading living Th17 lymphocytes, a process mediated by expression of activation-dependent lectin and its T cell-binding partner, N-acetyl-D-glucosamine (GlcNAc). Stable engulfment resulted in the death of the engulfed cells, and, remarkably, enhancement of GlcNAc exposure on T cells in the CNS ameliorated clinical EAE symptoms. These findings demonstrate the ability of myeloid cells to directly react to pathogenic T cell infiltration by engulfing living T cells. Amelioration of EAE via GlcNAc treatment suggests a novel first-defense pathway of myeloid cells as an initial response to CNS invasion and demonstrates that T cell engulfment by myeloid cells can be therapeutically exploited in vivo.
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PMID:CNS-localized myeloid cells capture living invading T cells during neuroinflammation. 3221 36