Diseases Commons^™

Impacts Of Population Level Environmental Contaminants, Sex Hormones, And Fibroblast Cell Subsets On Systemic Sclerosis (Ssc), Noelle N. Kosarek

Dartmouth College Ph.D Dissertations

Systemic sclerosis (SSc) is a rare autoimmune disease characterized by fibrosis of the skin and internal organs, vascular abnormalities, and autoantibody formation. The etiology of SSc is unknown, though the disease is thought to arise in genetically predisposed individuals after exposure to an environmental factor. There are few FDA approved disease modifying medications available to treat SSc.

The express aims of this dissertation are tripart. First, we aimed to validate a 3D tissue model known as the self-assembled skin equivalent (saSE) model. Second, we sought to describe the geographic distribution of SSc in a US Medicare population to better understand …

Autoimmune Susceptibility Imposed By Public Tcrβ Chains, Yunqian Zhao

Theses and Dissertations (ETD)

The major histocompatibility complex (MHC) is the strongest genetic risk factor for autoimmunity. It acts together with a corresponding TCR repertoire, yet, considering the extent of the repertoire's diversity, how this imposes disease susceptibility on a population is not well understood. We address the hypothesis that shared or public TCR, those present in most individuals, modulate autoimmune risk. High resolution analyses of autoimmune encephalomyelitis-associated T-cell receptor β chain (TCRβ) showed preferential utilization of public TCR sequences, implicating them in pathogenesis. Disease-associated public TCRβ, when transgenically expressed in association with endogenously rearranged T-cell receptor α chain (TCRα), could further endow unprimed …

Humanized Chimeric Receptors In The Therapy Of Multiple Sclerosis, Ioana Moisini

Theses and Dissertations (ETD)

The role of autoreactive, antigen-specific T-cells in the development of autoimmunity has long been documented. T-cells expressing chimeric receptors are specifically redirected against such cells and have been proven to suppress autoimmune encephalomyelitis, the murine model of multiple sclerosis. We here demonstrate the ability of humanized chimeric receptors to suppress experimental autoimmune encephalomyelitis (EAE) in a humanized mouse model by redirecting T lymphocytes against autoreactive T-cells. The receptors were synthesized by linking the 84-102 epitope of human myelin basic protein (MBP) to the extracellular and transmembrane domains of the beta chain of human major histocompatibility complex (MHC) class II molecule …