MMP-Independent Role of TIMP-1 at the Blood Brain Barrier during Viral Encephalomyelitis
Infection of the CNS (central nervous system) with a sublethal neurotropic coronavirus (JHMV) induces a vigorous inflammatory response. CD4 + and CD8 + T cells are essential to control infectious virus but at the cost of tissue damage. An enigma in understanding the contribution of T cell subsets in...
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2013-10-01
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Online Access: | https://doi.org/10.1042/AN20130033 |
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doaj-415fab912ee94d8baea56f5e2f9a4eb92020-11-25T02:53:59ZengSAGE PublishingASN Neuro1759-09141759-90912013-10-01510.1042/AN2013003310.1042_AN20130033MMP-Independent Role of TIMP-1 at the Blood Brain Barrier during Viral EncephalomyelitisCarine Savarin0Cornelia C. Bergmann1David R. Hinton2Stephen A. Stohlman3 Department of Neurosciences NC–30, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, U.S.A. Department of Neurosciences NC–30, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, U.S.A. Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, U.S.A. Department of Neurosciences NC–30, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, U.S.A.Infection of the CNS (central nervous system) with a sublethal neurotropic coronavirus (JHMV) induces a vigorous inflammatory response. CD4 + and CD8 + T cells are essential to control infectious virus but at the cost of tissue damage. An enigma in understanding the contribution of T cell subsets in pathogenesis resides in their distinct migration pattern across the BBB (blood brain barrier). CD4 + T cells transiently accumulate within the perivascular space, whereas CD8 + T cells migrate directly into the CNS parenchyma. As MMPs (matrix metalloproteinases) facilitate migration across the glia limitans, specific expression of the TIMP (tissue inhibitor of MMPs)-1 by CD4 + T cells present in the perivascular cuffs suggested that TIMP-1 is responsible for stalling CD4 + T cell migration into the CNS parenchyma. Using TIMP-1 deficient mice, the present data demonstrate an increase rather than a decrease in CD4 + T cell accumulation within the perivascular space during JHMV infection. Whereas virus control was not affected by perivascular retention of CD4 + T cells, disease severity was decreased and associated with reduced IFN γ (interferon γ) production. Moreover, decreased CD4 + T cell recruitment into the CNS parenchyma of TIMP-1 deficient mice was not associated with impaired T cell recruiting chemokines or MMP expression, and no compensation by other TIMP molecules was identified. These data suggest an MMP-independent role of TIMP-1 in regulating CD4 + T cell access into the CNS parenchyma during acute JHMV encephalitis.https://doi.org/10.1042/AN20130033 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Carine Savarin Cornelia C. Bergmann David R. Hinton Stephen A. Stohlman |
spellingShingle |
Carine Savarin Cornelia C. Bergmann David R. Hinton Stephen A. Stohlman MMP-Independent Role of TIMP-1 at the Blood Brain Barrier during Viral Encephalomyelitis ASN Neuro |
author_facet |
Carine Savarin Cornelia C. Bergmann David R. Hinton Stephen A. Stohlman |
author_sort |
Carine Savarin |
title |
MMP-Independent Role of TIMP-1 at the Blood Brain Barrier during Viral Encephalomyelitis |
title_short |
MMP-Independent Role of TIMP-1 at the Blood Brain Barrier during Viral Encephalomyelitis |
title_full |
MMP-Independent Role of TIMP-1 at the Blood Brain Barrier during Viral Encephalomyelitis |
title_fullStr |
MMP-Independent Role of TIMP-1 at the Blood Brain Barrier during Viral Encephalomyelitis |
title_full_unstemmed |
MMP-Independent Role of TIMP-1 at the Blood Brain Barrier during Viral Encephalomyelitis |
title_sort |
mmp-independent role of timp-1 at the blood brain barrier during viral encephalomyelitis |
publisher |
SAGE Publishing |
series |
ASN Neuro |
issn |
1759-0914 1759-9091 |
publishDate |
2013-10-01 |
description |
Infection of the CNS (central nervous system) with a sublethal neurotropic coronavirus (JHMV) induces a vigorous inflammatory response. CD4 + and CD8 + T cells are essential to control infectious virus but at the cost of tissue damage. An enigma in understanding the contribution of T cell subsets in pathogenesis resides in their distinct migration pattern across the BBB (blood brain barrier). CD4 + T cells transiently accumulate within the perivascular space, whereas CD8 + T cells migrate directly into the CNS parenchyma. As MMPs (matrix metalloproteinases) facilitate migration across the glia limitans, specific expression of the TIMP (tissue inhibitor of MMPs)-1 by CD4 + T cells present in the perivascular cuffs suggested that TIMP-1 is responsible for stalling CD4 + T cell migration into the CNS parenchyma. Using TIMP-1 deficient mice, the present data demonstrate an increase rather than a decrease in CD4 + T cell accumulation within the perivascular space during JHMV infection. Whereas virus control was not affected by perivascular retention of CD4 + T cells, disease severity was decreased and associated with reduced IFN γ (interferon γ) production. Moreover, decreased CD4 + T cell recruitment into the CNS parenchyma of TIMP-1 deficient mice was not associated with impaired T cell recruiting chemokines or MMP expression, and no compensation by other TIMP molecules was identified. These data suggest an MMP-independent role of TIMP-1 in regulating CD4 + T cell access into the CNS parenchyma during acute JHMV encephalitis. |
url |
https://doi.org/10.1042/AN20130033 |
work_keys_str_mv |
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