Emily K. Reinke
University of Wisconsin-Madison
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Publication
Featured researches published by Emily K. Reinke.
Journal of Immunology | 2007
Alla L. Zozulya; Emily K. Reinke; Dana C. Baiu; Jozsef Karman; Matyas Sandor; Zsuzsanna Fabry
Dendritic cells (DCs) accumulate in the CNS during inflammatory diseases, but the exact mechanism regulating their traffic into the CNS remains to be defined. We now report that MIP-1α increases the transmigration of bone marrow-derived, GFP-labeled DCs across brain microvessel endothelial cell monolayers. Furthermore, occludin, an important element of endothelial tight junctions, is reorganized when DCs migrate across brain capillary endothelial cell monolayers without causing significant changes in the barrier integrity as measured by transendothelial electrical resistance. We show that DCs produce matrix metalloproteinases (MMP) -2 and -9 and GM6001, an MMP inhibitor, decreases both baseline and MIP-1α-induced DC transmigration. These observations suggest that DC transmigration across brain endothelial cell monolayers is partly MMP dependent. The migrated DCs express higher levels of CD40, CD80, and CD86 costimulatory molecules and induce T cell proliferation, indicating that the transmigration of DCs across brain endothelial cell monolayers contributes to the maintenance of DC Ag-presenting function. The MMP dependence of DC migration across brain endothelial cell monolayers raises the possibility that MMP blockers may decrease the initiation of T cell recruitment and neuroinflammation in the CNS.
Clinical and Vaccine Immunology | 2003
Diane Sewell; Emily K. Reinke; Dominic O. Co; Laura H. Hogan; Robert B. Fritz; Matyas Sandor; Zsuzsa Fabry
ABSTRACT Infectious agents have been proposed to influence susceptibility to autoimmune diseases such as multiple sclerosis. We induced a Th1-mediated central nervous system (CNS) autoimmune disease, experimental autoimmune encephalomyelitis (EAE) in mice with an ongoing infection with Mycobacterium bovis strain bacillus Calmette-Guérin (BCG) to study this possibility. C57BL/6 mice infected with live BCG for 6 weeks were immunized with myelin oligodendroglial glycoprotein peptide (MOG35-55) to induce EAE. The clinical severity of EAE was reduced in BCG-infected mice in a BCG dose-dependent manner. Inflammatory-cell infiltration and demyelination of the spinal cord were significantly lessened in BCG-infected animals compared with uninfected EAE controls. ELISPOT and gamma interferon intracellular cytokine analysis of the frequency of antigen-specific CD4+ T cells in the CNS and in BCG-induced granulomas and adoptive transfer of MOG35-55-specific green fluorescent protein-expressing cells into BCG-infected animals indicated that nervous tissue-specific (MOG35-55) CD4+ T cells accumulate in the BCG-induced granuloma sites. These data suggest a novel mechanism for infection-mediated modulation of autoimmunity. We demonstrate that redirected trafficking of activated CNS antigen-specific CD4+ T cells to local inflammatory sites induced by BCG infection modulates the initiation and progression of a Th1-mediated CNS autoimmune disease.
Journal of Immunology | 2008
JangEun Lee; Emily K. Reinke; Alla L. Zozulya; Matyas Sandor; Zsuzsanna Fabry
Multiple sclerosis and an animal model resembling multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), are inflammatory demyelinating diseases of the CNS that are suppressed by systemic mycobacterial infection in mice and BCG vaccination in humans. Host defense responses against Mycobacterium in mice are influenced by T lymphocytes and their cytokine products, particularly IFN-γ, which plays a protective regulatory role in EAE. To analyze the counter-regulatory role of mycobacterial infection-induced IFN-γ in the CNS on the function of the pathological Th17 cells and the clinical outcome of EAE, we induced EAE in mice that were intracerebrally infected with Mycobacterium bovis bacille Calmette-Guerin (BCG). In this study, we demonstrate that intracerebral (i.c.) BCG infection prevented inflammatory cell recruitment to the spinal cord and suppressed the development of EAE. Concomitantly, there was a significant decrease in the frequency of myelin oligodendrocyte glycoprotein-specific IFN-γ-producing CD4+ T cells in the CNS. IL-17+CD4+ T cell responses were significantly suppressed in i.c. BCG-infected mice following EAE induction regardless of T cell specificity. The frequency of Foxp3+CD4+ T cells in these mice was equivalent to that of control mice. Intracerebral BCG infection-induced protection of EAE and suppression of myelin oligodendrocyte glycoprotein-specific IL-17+CD4+ T cell responses were similar in both wild-type and IFN-γ-deficient mice. These data show that live BCG infection in the brain suppresses CNS autoimmunity. These findings also reveal that the regulation of Th17-mediated autoimmunity in the CNS can be independent of IFN-γ-mediated mechanisms.
Journal of Neuroimmunology | 2006
Emily K. Reinke; Matthew J. Johnson; Changying Ling; Jozsef Karman; JangEun Lee; Joel V. Weinstock; Matyas Sandor; Zsuzsa Fabry
Substance P (SP) is a modulatory, pro-inflammatory neuropeptide. We investigated the role of the SP receptor, neurokinin-1 (NK-1), in EAE. Our data show that in the chronic phase, mice lacking NK-1 have improved mobility and decreased numbers of LFA-1 high CD4+ T cells and MOG-specific, IFN-gamma producing CD4+ T cells. SR140333, an NK-1 antagonist, administered alone during the chronic phase of EAE was not sufficient to ameliorate symptoms. These results indicate that SP, through NK-1, contributes to maintenance of CNS inflammation, and combining NK-1 antagonists with conventional anti-inflammatory treatments may enhance the success of treatments for diseases like multiple sclerosis.
Future Neurology | 2007
Alla L. Zozulya; Emily K. Reinke; Changying Ling; Matyas Sandor; Zsuzsanna Fabry
Dendritic cells (DCs) are essential antigen-presenting cells responsible for initiating cellular immune responses. The increasing interest in the mechanisms of DC trafficking has created new and exciting opportunities for bench-to-bedside therapies to treat autoimmune diseases of the central nervous system (CNS). However, tracking the migration of DCs in the CNS has proved to be more problematic owing to their low number in the immunologically privileged environment of the brain and high diversity as a cell population. A significant contributor to immune privilege in the brain is the blood–brain barrier, a unique structure recognized to regulate the entry of immune cells into the brain. Currently, it is hypothesized that the migration of DCs across the blood–brain barrier is critically important for the initiation of immune responses of CNS autoimmunity. This review summarizes the present knowledge on DC trafficking in the CNS and the main functions of these cells in initiating CNS autoimmunity. Selective...
International Immunology | 2003
Diane Sewell; Zhu Qing; Emily K. Reinke; David Elliot; Joel V. Weinstock; Matyas Sandor; Zsuzsa Fabry
Immunology Letters | 2002
Diane Sewell; Emily K. Reinke; Laura H. Hogan; Matyas Sandor; Zsuzsa Fabry
Immunology Letters | 2006
Emily K. Reinke; Zsuzsa Fabry
Neurobiology of Aging | 2006
Pamela R. Westmark; Hyun Cheol Shin; Cara J. Westmark; Syrus R. Soltaninassab; Emily K. Reinke; James S. Malter
Journal of Neuroimmunology | 2007
Emily K. Reinke; JangEun Lee; Alla L. Zozulya; Jozsef Karman; William A. Muller; Matyas Sandor; Zsuzsanna Fabry