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Full-Text Articles in Life Sciences

The Role Of Notch3 Signaling In T Helper Cell Differentiation And Induction Of Eae, Furkan Ayaz Mar 2016

The Role Of Notch3 Signaling In T Helper Cell Differentiation And Induction Of Eae, Furkan Ayaz

Doctoral Dissertations

Th1 and Th17 are subsets of CD4+ T cells or T helper cells (Th). Th cells are the major adaptive immune cells involved in inflammation during the development of Multiple Sclerosis (MS). MS is a neurodegenerative autoimmune disease and one mouse model of the disease is Experimental Autoimmune Encephalomyelitis (EAE). Development and differentiation of Th1 and Th17 cells are regulated by the Notch family of trans-membrane proteins (Notch1, 2, 3 and 4). We and others have shown that pharmacological inhibition of Notch activity impairs Th1 and Th17 differentiation as well as development of EAE. However, it is not known which ...


Elucidating Cellular Signaling Pathways That Contribute To The Immunopathogenesis Of Aplastic Anemia, Christina M. Kuksin Nov 2014

Elucidating Cellular Signaling Pathways That Contribute To The Immunopathogenesis Of Aplastic Anemia, Christina M. Kuksin

Doctoral Dissertations

Aplastic Anemia is a rare immune mediated bone marrow failure disease that is mediated by autoreactive T cells that cause destruction to the stem, progenitor, and stromal cells in the bone marrow. Because little is known about the etiology of the disease, our lab has developed a major MHC mismatch GVHD model to examine cellular pathways in autoreactive T cells that contribute to disease. We examined three pathways that are important in T cell activation and differentiation and asked if they were important in the development of Aplastic Anemia. First, we were able to show that expression of active PKCθ ...


The Role Of Notch In Th17 Differentiation, Reem Suleiman Sep 2013

The Role Of Notch In Th17 Differentiation, Reem Suleiman

Open Access Dissertations

Th17 cells are pro-inflammatory cells that are characterized by the production of their signature cytokine, IL-17. Although they are thought to have arisen to protect against extracellular bacteria and fungi they have been shown to mediate autoimmune diseases such as EAE and psoarisis. Notch protein is a cell-surface receptor that has been widely conserved among species. It plays an essential role in determining multiple cell fates. More recently, it has been implicated in regulating peripheral CD4+ T-cell responses. In these studies, we report that blockade of Notch signaling significantly down-regulates the production of IL-17 and associated cytokines in both mouse ...


The Roles Of Notch1 And Pkc-Θ In Immune Mediated Bone Marrow Failure, Justine E. Roderick May 2011

The Roles Of Notch1 And Pkc-Θ In Immune Mediated Bone Marrow Failure, Justine E. Roderick

Open Access Dissertations

We sought to evaluate the individual contributions of Notch1 and PKC-ζ to disease progression in a mouse model of immune-mediated bone marrow failure and to define a mechanism for their potential cellular cooperation. We transferred parental bulk splenocytes into F1-hybrid recipients to induce a robust immune-mediated bone marrow failure (BMF) that we could partially rescue by administering a pharmacological inhibitor of Notch activation. Transferring splenocytes from PKC--ζ-/- animals did not induce disease, and treating animals with a pharmacological inhibitor of PKC-ζ also provided full protection from disease. We found that inhibiting Notch1 resulted in PKC-ζ down-regulation, and blocking PKC-ζ reduced ...


Notch1 Modulation Of Lymphoid Target Genes, Ok Hyun Cho Sep 2009

Notch1 Modulation Of Lymphoid Target Genes, Ok Hyun Cho

Open Access Dissertations

Over the past decades, information has accumulated concerning the mechanism how an exterior signal induced by ligand on neighboring cells is transmitted to the nucleus through the Notch receptor and the cellular effects of Notch signaling on the regulation of differentiation, proliferation and apoptosis in many cell types. However, the function and the mechanism of Notch signaling in peripheral T cells still remains to be addressed. Therefore, we asked whether Notch1 is involved in CD8+ cytolytic effector T cell (CTLs) maturation and effector functions and how Notch1 exerts its cellular function in the nucleus and in the cytoplasm. The maturation ...