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Home > Mathematics and Science Textbooks > Biology, life sciences > Icos Operates Through Multiple Pathways to Regulate the Magnitude of Th2-Mediated Inflammation in Vivo
Icos Operates Through Multiple Pathways to Regulate the Magnitude of Th2-Mediated Inflammation in Vivo

Icos Operates Through Multiple Pathways to Regulate the Magnitude of Th2-Mediated Inflammation in Vivo


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About the Book

Inducible Costimulator (ICOS) is an important regulator of Th2 lymphocyte function and a potential immunotherapeutic target for allergy and asthma. A SNP in the ICOS 5' promoter in humans is associated with increased atopy and increased ICOS surface expression and Th2 cytokine production from peripheral blood mononuclear cells. However, it is not known if increased ICOS expression is a result of disease pathology or if it contributes to disease progression. We developed a mouse model in which ICOS expression levels are genetically predetermined in order to test our hypothesis that genetic regulation of ICOS expression controls the severity of Th2 responses in vivo . Using ICOS+/+ and ICOS+/- mice in a Th2 model of airway inflammation, we found that T cells from the ICOS +/+ mice had reduced ICOS expression and decreased Th2-mediated airway inflammation inflammation in vivo. However, it is not known whether this decrease is due to the established defect in Th2 differentiation of ICOS-/- T cells alone, or if it is compounded by defective migration of these cells. We hypothesized that a defect in migration may contribute to the weaker Th2 response in ICOS-/- mice. Thus we compared chemokine receptor expression of ICOS-/- and ICOS +/+ T cells upon in vitro and in vivo stimulation. Interestingly, ICOS-/- T cells did not down-regulate CCR7 as well as ICOS +/+ T cells when stimulated in vitro only under Th2-skewing conditions. Furthermore, at the peak of Th2-mediated inflammation ICOS-/- CD4+ effector T cells consistently have a higher expression of CCR7 than ICOS+/+ CD4+ effector T cells. As dendritic cells are the primary initiators of the immune response we hypothesized that ICOS costimulation can influence dendritic cells at different stages of the immune response. I demonstrate that in ICOS-/- mice naive splenic dendritic cells fail to down regulate B7RP-1, and at the peak of an airway inflammation model, ICOS-/- mice had a decreased percentage of activated dendritic cells in the lung tissue compared to wild type mice. These data suggest ICOS expression regulates the magnitude of the in vivo Th2 response, perhaps by influencing Th2 differentiation, Th2 cell migration or lung dendritic cells.


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Product Details
  • ISBN-13: 9781243499035
  • Publisher: Proquest, Umi Dissertation Publishing
  • Publisher Imprint: Proquest, Umi Dissertation Publishing
  • Height: 246 mm
  • Weight: 263 gr
  • ISBN-10: 1243499036
  • Publisher Date: 01 Sep 2011
  • Binding: Paperback
  • Spine Width: 8 mm
  • Width: 189 mm


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Icos Operates Through Multiple Pathways to Regulate the Magnitude of Th2-Mediated Inflammation in Vivo
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Icos Operates Through Multiple Pathways to Regulate the Magnitude of Th2-Mediated Inflammation in Vivo
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