Antibody targeting of the CC chemokine ligand 5 results in diminished leukocyte infiltration into the central nervous system and reduced neurologic disease in a viral model of multiple sclerosis.
William G. Glass,Michelle J. Hickey,Jenny L. Hardison,Michael T. Liu,Jerry E. Manning,Thomas E. Lane +5 more
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TLDR
The severity of CNS disease can be reduced through the use of a neutralizing mAb directed against CCL5 in a viral model of demyelination, demonstrating the ability to differentially target select populations of T cells.Abstract:
Intracerebral infection of mice with mouse hepatitis virus, a member of the Coronaviridae family, reproducibly results in an acute encephalomyelitis that progresses to a chronic demyelinating disease. The ensuing neuropathology during the chronic stage of disease is primarily immune mediated and similar to that of the human demyelinating disease multiple sclerosis. Secretion of chemokines within the CNS signals the infiltration of leukocytes, which results in destruction of white matter and neurological impairment. The CC chemokine ligand (CCL)5 is localized in white matter tracts undergoing demyelination, suggesting that this chemokine participates in the pathogenesis of disease by attracting inflammatory cells into the CNS. In this study, we administer a mAb directed against CCL5 to mice with established mouse hepatitis virus-induced demyelination and impaired motor skills. Anti-CCL5 treatment decreased T cell accumulation within the CNS based, in part, on viral Ag specificity, indicating the ability to differentially target select populations of T cells. In addition, administration of anti-CCL5 improved neurological function and significantly (p ≤ 0.005) reduced the severity of demyelination and macrophage accumulation within the CNS. These results demonstrate that the severity of CNS disease can be reduced through the use of a neutralizing mAb directed against CCL5 in a viral model of demyelination.read more
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Chemokines and their receptors: drug targets in immunity and inflammation.
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Trafficking of immune cells in the central nervous system.
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Interference with Heparin Binding and Oligomerization Creates a Novel Anti-Inflammatory Strategy Targeting the Chemokine System
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References
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TL;DR: At a given time point of the disease, the patterns of demyelination were heterogeneous between patients, but were homogenous within multiple active lesions from the same patient, suggesting that MS may be a disease with heterogeneous pathogenetic mechanisms.
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Journal ArticleDOI
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Torben Lykke Sørensen,Marie Tani,Jakob Søndergaard Jensen,Virginia Pierce,Claudia F. Lucchinetti,Virginia A Folcik,Shixin Qin,James B. Rottman,Finn Sellebjerg,Robert M. Strieter,Jette L. Frederiksen,Richard M. Ransohoff +11 more
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