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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Blood coagulation protein fibrinogen promotes autoimmunity and demyelination via chemokine release and antigen presentation
Nature Communications, Volume 6, Article 8164, Year 2015
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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. © 2015 Macmillan Publishers Limited.
Authors & Co-Authors
Ryu, Jae-kyu
United States, San Francisco
Gladstone Institute of Neurological Disease
Petersen, Mark Adam
United States, San Francisco
Gladstone Institute of Neurological Disease
United States, San Francisco
University of California, San Francisco
Prod'homme, Thomas
United States, San Francisco
University of California, San Francisco
Lassmann, Hans P.
Austria, Vienna
Medizinische Universität Wien
Statistics
Citations: 202
Authors: 4
Affiliations: 5
Identifiers
Doi:
10.1038/ncomms9164
ISSN:
20411723