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Fibrinogen promotes autoimmunity and demyelination via chemokine release and antigen presentation [Mm]

ABSTRACT: Determination of the mechanism by which fibrinogen, a central blood coagulation protein drives immunological responses targeted to the CNS. Results identify the factors involved in the regulation and provide mechanistic basis. We subjected fibrinogen-injected corpus callosum to microarray to determine the genes involved in innate and adaptive immune responses by fibrinogen deposited in the CNS after blood-brain barrier disruption.

ORGANISM(S): Mus musculus

PROVIDER: GSE71082 | GEO | 2015/09/16

SECONDARY ACCESSION(S): PRJNA290324

REPOSITORIES: GEO

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Fibrinogen promotes autoimmunity and demyelination via chemokine release and antigen presentation [Mm]

Project description:Determination of the mechanism by which fibrinogen, a central blood coagulation protein drives immunological responses targeted to the CNS. Results identify the factors involved in the regulation and provide mechanistic basis. We subjected fibrinogen-injected corpus callosum to microarray to determine the genes involved in innate and adaptive immune responses by fibrinogen deposited in the CNS after blood-brain barrier disruption. Corpus callosum tissues were isolated from mice received stereotactic injection of fibrinogen or ACSF at 12 hr. Tissues were subjected for RNA extraction and hybridization on Affymatrix microarrays. Two ACSF and two fibrinogen samples were generated.

2015-09-16 | E-GEOD-71082 | biostudies-arrayexpress

Fibrinogen promotes autoimmunity and demyelination via chemokine release and antigen presentation [Rn]

Project description:Determination of the mechanism by which fibrinogen, a central blood coagulation protein drives immunological responses targeted to the CNS. Results identify the factors involved in the regulation and provide mechanistic basis. We subjected fibrin-stimulated microglia to microarray to determine the genes involved in innate and adaptive immune responses by fibrinogen deposited in the CNS after blood-brain barrier disruption. Rat microglia were stimulated with fibrin for 6 hr and subjected for RNA extraction and hybridization on Affymatrix microarrays. Two unstimulated and two fibrin-stimulated samples were generated.

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Fibrinogen promotes autoimmunity and demyelination via chemokine release and antigen presentation [Rn]

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Fibrinogen promotes autoimmunity and demyelination via chemokine release and antigen presentation

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-09-16 | E-GEOD-71084 | biostudies-arrayexpress

Fibrinogen promotes autoimmunity and demyelination via chemokine release and antigen presentation

Project description:This SuperSeries is composed of the SubSeries listed below.

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Blood coagulation protein fibrinogen promotes autoimmunity and demyelination via chemokine release and antigen presentation.

Project description:Autoimmunity and macrophage recruitment into the central nervous system (CNS) are critical determinants of neuroinflammatory diseases. However, the mechanisms that drive immunological responses targeted to the CNS remain largely unknown. Here we show that fibrinogen, a central blood coagulation protein deposited in the CNS after blood-brain barrier disruption, induces encephalitogenic adaptive immune responses and peripheral macrophage recruitment into the CNS leading to demyelination. Fibrinogen stimulates a unique transcriptional signature in CD11b(+) antigen-presenting cells inducing the recruitment and local CNS activation of myelin antigen-specific Th1 cells. Fibrinogen depletion reduces Th1 cells in the multiple sclerosis model, experimental autoimmune encephalomyelitis. Major histocompatibility complex (MHC) II-dependent antigen presentation, CXCL10- and CCL2-mediated recruitment of T cells and macrophages, respectively, are required for fibrinogen-induced encephalomyelitis. Inhibition of the fibrinogen receptor CD11b/CD18 protects from all immune and neuropathologic effects. Our results show that the final product of the coagulation cascade is a key determinant of CNS autoimmunity.

| S-EPMC4579523 | biostudies-literature

Fibrinogen activates BMP signaling in oligodendrocyte progenitor cells (OPCs) and inhibits remyelination after vascular damage [Rat_OPC_48h_Fibrinogen]

Project description:Determination of the mechanism by which fibrinogen, a central blood coagulation protein, regulates OPC functions and remyelination in the CNS. We used microarrays to determine the genes involved in OPC responses to fibrinogen, which is deposited in the CNS after blood-brain barrier disruption.

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Fibrinogen activates BMP signaling in oligodendrocyte progenitor cells (OPCs) and inhibits remyelination after vascular damage [Rat_OPC_12h_Fibrinogen]

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Fibrinogen is upregulated following kidney damage and protects it against ischemia-reperfusion injury

Project description:characterization of fibrinogen expression in the kidney, excretion in the urine following kidney damage and evaluating the therapeutic potential of fibrinogen in acute kidney injury.

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