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Full-Text Articles in Life Sciences
Canonical Notch Signaling Positively Regulates Mir-155 Transcription In A Nfκb-Dependent Manner, Joe Torres
Canonical Notch Signaling Positively Regulates Mir-155 Transcription In A Nfκb-Dependent Manner, Joe Torres
Doctoral Dissertations
MicroRNA-155 (miR-155) is an important pro-inflammatory molecule that controls immune responses in both physiological and pathological settings. Although miR-155 is well studied, little is known about its transcriptional regulation in T cells. We sought to further understand the mechanisms by which miR-155 transcription is induced following T cell activation. We found that miR-155 transcription is dependent on the activity of the Notch and NFkB signaling pathways. It was determined that the canonical Notch signaling pathway was involved in this regulation and that it was dependent upon the activation of NFkB. Additional work confirmed that both NFkB and Notch1 directly bind …
The Role Of Notch3 Signaling In T Helper Cell Differentiation And Induction Of Eae, Furkan Ayaz
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 …
Elucidating Cellular Signaling Pathways That Contribute To The Immunopathogenesis Of Aplastic Anemia, Christina M. Kuksin
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 …
Non-Canonical Notch Signaling Regulates Activation And Differentiation Of Peripheral Cd4+ T Cells, Anushka Dongre
Non-Canonical Notch Signaling Regulates Activation And Differentiation Of Peripheral Cd4+ T Cells, Anushka Dongre
Doctoral Dissertations
Cleavage of the Notch receptor via a γ-secretase, results in the release of the active intra-cellular domain of Notch that migrates to the nucleus and interacts with RBP-JΚ, resulting in the activation of downstream target genes. This canonical Notch signaling pathway has been documented to influence T-cell development and function. However, the mechanistic details underlying this process remain obscure. In addition to RBP-JΚ, the intra-cellular domain of Notch also interacts with other proteins in the cytoplasm and nucleus, giving rise to the possibility of an alternate, RBP-JΚ independent Notch pathway. However, the contribution of such RBP-J …
Notch1 Modulation Of Lymphoid Target Genes, Ok Hyun Cho
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 …