voner
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here is a summary:
http://loonylabs.org/2015/10/10/blood-clotting-protein-immune-attack-on-the-brain/
some quotes from the article:
In the current study, the scientists created a new animal model of disease to determine if BBB leakage can cause autoimmunity. They discovered that injecting just one drop of blood into the brain set off the brain’s immune response, kick-starting a chain reaction that resulted in inflammation and myelin damage. Myelin is the protective sheath that insulates nerve fibers in the brain, and it is the primary site of injury in MS. What’s more, the scientists were able to pinpoint a specific protein in the blood, the blood-clotting factor fibrinogen, as the trigger for the disease-causing process.........
......“These findings question a long-held paradigm that myelin-specific T cells initiate inflammation in the brain through activation of microglia and brain macrophages,” says Scott Zamvil, MD, PhD, a professor of neurology at the University of California, San Francisco and co-author on the paper.
“This study demonstrates that the original paradigm may also occur in reverse. Namely, initial activation of microglia and brain macrophages may activate T cells.”......
so from what I read they think that fibriogen (from the blood) is deposited as fibrin, which triggers an neuroinflammation cascade and seems to induce an autoimmune response.... I think it's very interesting that the findings cast doubt on the belief that T cells initiate the autoimmune response.
it is a open access paper – here it is:
http://www.nature.com/ncomms/2015/150910/ncomms9164/full/ncomms9164.html
here is the abstract( my bold emphasis added):
Autoimmunity and macrophage recruitment into the central nervous system (CNS) are cri-
tical 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 tran-
scriptional signature in CD11b þ 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.
Comments anyone? @Marco @Jonathan Edwards
http://loonylabs.org/2015/10/10/blood-clotting-protein-immune-attack-on-the-brain/
some quotes from the article:
In the current study, the scientists created a new animal model of disease to determine if BBB leakage can cause autoimmunity. They discovered that injecting just one drop of blood into the brain set off the brain’s immune response, kick-starting a chain reaction that resulted in inflammation and myelin damage. Myelin is the protective sheath that insulates nerve fibers in the brain, and it is the primary site of injury in MS. What’s more, the scientists were able to pinpoint a specific protein in the blood, the blood-clotting factor fibrinogen, as the trigger for the disease-causing process.........
......“These findings question a long-held paradigm that myelin-specific T cells initiate inflammation in the brain through activation of microglia and brain macrophages,” says Scott Zamvil, MD, PhD, a professor of neurology at the University of California, San Francisco and co-author on the paper.
“This study demonstrates that the original paradigm may also occur in reverse. Namely, initial activation of microglia and brain macrophages may activate T cells.”......
so from what I read they think that fibriogen (from the blood) is deposited as fibrin, which triggers an neuroinflammation cascade and seems to induce an autoimmune response.... I think it's very interesting that the findings cast doubt on the belief that T cells initiate the autoimmune response.
it is a open access paper – here it is:
http://www.nature.com/ncomms/2015/150910/ncomms9164/full/ncomms9164.html
here is the abstract( my bold emphasis added):
Autoimmunity and macrophage recruitment into the central nervous system (CNS) are cri-
tical 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 tran-
scriptional signature in CD11b þ 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.
Comments anyone? @Marco @Jonathan Edwards
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