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.
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.
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.
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.
Project description:A number of autoimmunity-associated MHC class II proteins interact only weakly with the invariant chain-derived class II-associated invariant chain peptide (CLIP). CLIP dissociates rapidly from I-Ag7 even in the absence of DM, and this property is related to the type 1 diabetes-associated b57 polymorphism. We generated knock-in Non-obese Diabetic (NOD) mice with a single amino acid change in the CLIP segment of invariant chain in order to moderately slow CLIP dissociation from I-Ag7. These knock-in mice had a significantly reduced incidence of spontaneous type 1 diabetes and diminished islet infiltration by CD4 T cells, in particular T cells specific for fusion peptides generated by covalent linkage of proteolytic fragments within b cell secretory granules. Rapid CLIP dissociation enhanced presentation of such extracellular peptides, thus bypassing the conventional MHC class II antigen processing pathway. Autoimmunity-associated MHC class II polymorphisms therefore not only modify binding of self-peptides, but also alter the biochemistry of peptide acquisition.