Off-campus UMass Amherst users: To download campus access dissertations, please use the following link to log into our proxy server with your UMass Amherst user name and password.
Non-UMass Amherst users: Please talk to your librarian about requesting this dissertation through interlibrary loan.
Dissertations that have an embargo placed on them will not be available to anyone until the embargo expires.
Author ORCID Identifier
Open Access Dissertation
Doctor of Philosophy (PhD)
Molecular and Cellular Biology
Year Degree Awarded
Month Degree Awarded
Barbara A. Osborne
Immunology and Infectious Disease
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 Notch family member or members play a major role in this process. In this thesis, by using Notch3 knockout mice, we demonstrate that Notch3 is one of the major regulatory members of Notch signaling that is involved in regulation of Th1, Th2, iTreg and Th17 polarization as well as pro-inflammatory cytokine GMCSF production by Th cells. Impaired Notch3 signaling did not affect Th cell activation and proliferation. Our results demonstrate a previously unknown role of Notch3 in the development of pro-inflammatory Th cell types. We also report that non-canonical Notch signaling through PKCθ may play an important role in Th17 differentiation. Development of EAE was not affected by impaired Notch3 signaling which suggests a compensation mechanism by other Notch protein(s) that regulate the development of EAE in vivo.
Ayaz, Furkan, "The Role of NOTCH3 Signaling in T Helper Cell Differentiation and Induction of EAE" (2016). Doctoral Dissertations. 549.