Advisor(s)

Hongwei Qin

Committee Member(s)

Andre Ballesteros-Tato
Ashley Harms
Chander Raman
Hongwei Qin
Michelle Gray

Document Type

Dissertation

Date of Award

6-1-2026

Degree Name

Doctor of Philosophy (PhD)

School

Joint Health Sciences (Interdisciplinary)

Department

Microbiology

Abstract

Multiple sclerosis (MS) is a chronic, debilitating autoimmune disorder which results in neurodegeneration within the central nervous system (CNS) encompassing the brain and spinal cord. Previously, MS was thought to be primarily T-cell mediated, however the recent efficacy of B-cell depletion therapies in MS patients has revealed B-cells play critical roles in MS pathology. However, the mechanisms by which B-cell contribution manifests remain poorly understood. My dissertation study suggests a mechanism behind B-cell dysregulation in MS patients and the MS murine model, Experimental Autoimmune Encephalomyelitis (EAE), through Blimp1-deficiency in follicular regulatory T cells (TFR). neuritin, a neurotrophic factor, recently revealed to regulate production of GC B cells, plasma cell (PC) differentiation, and IgE production in allergy. Our data suggests that neuritin expression in TFR cells is dependent on the activity of Blimp1 as a transcription factor. The ability of B cells to interact with T cells and IgG contribution to MS pathology has already been strongly implicated. However, IgE, classically known for involvement in allergy and allergy-mediated chronic disorders, has only recently been implicated in several autoimmune disorders. The contribution of IgE to MS pathology has yet to be explored in depth. IgE is known to bind its cognate high-affinity receptor, FcεRI, which is predominantly expressed on mast cells and basophils. Dendritic cells and macrophages have also been shown to express FcεRI, however how this receptor functions or potentially regulates the response of these cells is unclear. Intriguingly, this study identifies and characterizes a subset, FcεRIα+ macrophages, both in the periphery and within the CNS at homeostasis, where they exhibit a unique phenotype of increased susceptibility towards inflammatory responses and specific CNS niche specificity. My findings suggest that FcεRIα+ macrophages are predisposed to heightened inflammatory activity in the context of neuroinflammation, while demonstrating the ability to control tumor growth in immunosuppressive environments.

Keywords

FcεRI;germinal center;IgE;macrophage;MS;TFR cell

Download

Available for download on Saturday, June 01, 2126

Share

COinS