Emma Wilson

Publications (35) View all

• Article: Visualizing chemokine-dependent T cell activation and migration in response to central nervous system infection.

  Monica J Carson, Emma H Wilson
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  ABSTRACT: In response to central nervous system (CNS) injury and infection, astrocytes, neurons, and CNS vasculature express several chemokines, including CCL21. Quantitative polymerase chain reaction (qPCR), western blot, and immunohistochemical methods can quantify mRNA and protein expression. However, these methods do not quantify chemokine bioavailability and bioactivity, variables modified by many environmental factors including composition of the extracellular matrix (ECM). Here we illustrate how two-photon microscopy and carboxyfluorescein succinimidyl ester (CFSE or CFDA SE) labeling of T cells coupled with flow cytometry can be used as tools to assess chemokine-mediated regulation of T cell proliferation, activation, and migration.
  Methods in molecular biology (Clifton, N.J.) 01/2013; 1013:171-83.
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  Available from: Emma Wilson

  Article: β-Arrestin-2 mediates the proinflammatory effects of proteinase-activated receptor-2 in the airway.

  Heddie L Nichols, Mahmoud Saffeddine, Barbara S Theriot, Akhil Hegde, Daniel Polley, Tamer El-Mays, Harissios Vliagoftis, Morley D Hollenberg, Emma H Wilson, Julia K L Walker, Kathryn A Defea
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  ABSTRACT: Proteinase-Activated rreceptor-2 (PAR(2)), a G-protein-coupled Receptor, activated by serine proteinases, is reported to have both protective and proinflammatory effects in the airway. Given these opposing actions, both inhibitors and activators of PAR(2) have been proposed for treating asthma. PAR(2) can signal through two independent pathways: a β-arrestin-dependent one that promotes leukocyte migration, and a G-protein/Ca(2+) one that is required for prostaglandin E(2) (PGE(2)) production and bronchiolar smooth muscle relaxation. We hypothesized that the proinflammatory responses to PAR(2) activation are mediated by β-arrestins, whereas the protective effects are not. Using a mouse ovalbumin model for PAR(2)-modulated airway inflammation, we observed decreased leukocyte recruitment, cytokine production, and mucin production in β-arrestin-2(-/-) mice. In contrast, PAR(2)-mediated PGE(2) production, smooth muscle relaxation, and decreased baseline airway resistance (measures of putative PAR(2) "protective" effects) were independent of β-arrestin-2. Flow cytometry and cytospins reveal that lung eosinophil and CD4 T-cell infiltration, and production of IL-4, IL-6, IL-13, and TNFα, were enhanced in wild-type but not β-arrestin-2(-/-) mice. Using the forced oscillation technique to measure airway resistance reveals that PAR(2) activation protects against airway hyperresponsiveness by an unknown mechanism, possibly involving smooth muscle relaxation. Our data suggest that the PAR(2)-enhanced inflammatory process is β-arrestin-2 dependent, whereas the protective anticonstrictor effect of bronchial epithelial PAR(2) may be β-arrestin independent.
  Proceedings of the National Academy of Sciences 09/2012; 109(41):16660-5. · 9.68 Impact Factor
• Article: Stabilin-1 expression in tumor associated macrophages.

  Clément David, J Philip Nance, Jacqueline Hubbard, Mike Hsu, Devin Binder, Emma H Wilson
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  ABSTRACT: Glioblastoma multiforme is a very aggressive and common form of brain tumor. Current therapies consist of a combination of surgical removal, chemotherapy and radiation therapy. These drastic treatments still leave a current prognosis of median survival of less than 1 year. Lack of effectiveness of these treatments has left researchers looking for alternative forms of treatment. A significant alternative currently being investigated is the use of the immune system to potentially target and eliminate tumor cells directly. Stabilin-1, a scavenger receptor expressed by macrophages, has the potential in inhibiting tumor growth by binding and internalizing secreted protein acidic and rich in cysteine (SPARC). SPARC is known to be upregulated in the tumor microenvironment and is involved in extracellular matrix remodeling, cell proliferation and migration. Decreasing SPARC expression using siRNA has been shown to decrease tumor invasiveness and survival. We investigated the phenotype of stabilin-1 expressing immune cells in the tumor environment and demonstrated a transient population of alternatively activated macrophages expressing stabilin-1 in the tumor environment and the disappearance of that population as the tumor progresses.
  Brain research 08/2012; 1481:71-8. · 2.46 Impact Factor
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  Available from: Emma Wilson

  Article: Role of C-C chemokine receptor type 7 and its ligands during neuroinflammation.

  Shahani Noor, Emma H Wilson
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  ABSTRACT: For decades, chemokines and their receptors have received a great deal of attention for their multiple roles in controlling leukocyte functions during inflammation and immunity. The ability of chemokines to convey remarkably versatile but context-specific signals identifies them as powerful modulators of immune responses generated in response to diverse pathogenic or non-infectious insults. A number of recent studies have speculated that the C-C chemokine receptor type 7 (CCR7), plays important roles in immune-cell trafficking in various tissue compartments during inflammation and in immune surveillance. Using computational modeling and microfluidics-based approaches, recent studies have explored leukocyte migration behavior in response to CCR7 ligands in a complex chemokine environment existing with other coexisting chemokine fields. In this review, we summarize the current understanding of the effects of soluble versus immobilized ligands and of the downstream signaling pathways of CCR7 that control leukocyte motility, directionality, and speed. This review also integrates the current knowledge about the role of CCR7 in coordinating immune responses between secondary lymphoid organs and peripheral tissue microenvironments during primary or secondary antigen encounters. CCR7 seems to influence distinct immunological events during inflammatory responses in the central nervous system (CNS) including immune-cell entry and migration, and neuroglial interactions. The clinical and pathological outcome may vary depending on its contribution in the inflamed CNS microenvironment. Understanding these mechanisms has direct implications for therapeutic developments favoring more protective and efficient immune responses.
  Journal of Neuroinflammation 04/2012; 9:77. · 3.83 Impact Factor
• Article: CNS-derived CCL21 is both sufficient to drive homeostatic CD4+ T cell proliferation and necessary for efficient CD4+ T cell migration into the CNS parenchyma following Toxoplasma gondii infection.

  Corinne C Ploix, Shahani Noor, Janelle Crane, Kokoechat Masek, Whitney Carter, David D Lo, Emma H Wilson, Monica J Carson
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  ABSTRACT: Injury, infection and autoimmune triggers increase CNS expression of the chemokine CCL21. Outside the CNS, CCL21 contributes to chronic inflammatory disease and autoimmunity by three mechanisms: recruitment of lymphocytes into injured or infected tissues, organization of inflammatory infiltrates into lymphoid-like structures and promotion of homeostatic CD4+ T-cell proliferation. To test if CCL21 plays the same role in CNS inflammation, we generated transgenic mice with astrocyte-driven expression of CCL21 (GFAP-CCL21 mice). Astrocyte-produced CCL21 was bioavailable and sufficient to support homeostatic CD4+ T-cell proliferation in cervical lymph nodes even in the absence of endogenous CCL19/CCL21. However, lymphocytes and glial-activation were not detected in the brains of uninfected GFAP-CCL21 mice, although CCL21 levels in GFAP-CCL21 brains were higher than levels expressed in inflamed Toxoplasma-infected non-transgenic brains. Following Toxoplasma infection, T-cell extravasation into submeningeal, perivascular and ventricular sites of infected CNS was not CCL21-dependent, occurring even in CCL19/CCL21-deficient mice. However, migration of extravasated CD4+, but not CD8+ T cells from extra-parenchymal CNS sites into the CNS parenchyma was CCL21-dependent. CD4+ T cells preferentially accumulated at perivascular, submeningeal and ventricular spaces in infected CCL21/CCL19-deficient mice. By contrast, greater numbers of CD4+ T cells infiltrated the parenchyma of infected GFAP-CCL21 mice than in wild-type or CCL19/CCL21-deficient mice. Together these data indicate that CCL21 expression within the CNS has the potential to contribute to T cell-mediated CNS pathology via: (a) homeostatic priming of CD4+ T-lymphocytes outside the CNS and (b) by facilitating CD4+ T-cell migration into parenchymal sites following pathogenic insults to the CNS.
  Brain Behavior and Immunity 07/2011; 25(5):883-96. · 4.72 Impact Factor