GSBS Dissertations and Theses

ORCID ID

0000-0002-6411-5208

Approval Date

10-20-2017

Document Type

Doctoral Dissertation

Academic Program

Interdisciplinary Graduate Program

Department

Microbiology and Physiological Systems

First Thesis Advisor

Vladimir Litvak

Keywords

Neuroimmunology, T cells, social behavior, Microglia, Neurodegenerative disease, Rett syndrome, Systems biology

Abstract

Although the central nervous system was long perceived as the ivory tower without immune entities, there is growing evidence that the immune and nervous systems are intimated connected. These two systems have been shown to communicate both cellularly and molecularly under physiological and pathological conditions. Despite our increasing understanding of the interplay between these two systems, there are still numerous open questions. In this thesis, I address such unanswered questions related to: the role of microglia and their mechanism in contributing to pathologies in Rett syndrome; the beneficial effects of T-cell secreted cytokines in supporting social brain function; the evolutionary link of the interactions between the nervous and immune systems; the transcription regulation of a subset of microglia population in common neurodegenerative diseases.

Collectively, the current thesis is focused on the joint frontier of bioinformatics and experimental work in neuroimmunology. A multifaceted approach, that includes transcriptomics, genomics and other biomolecular modules, was implemented to unearth signaling pathways and mechanisms underlying the presenting biological phenomena. The findings of this thesis can be summarized as follows: 1) MeCP2 acts as a master regulator in the transcriptional repression of inflammatory stimuli in macrophages; 2) T-cell secreted IFN-γ supports social brain function through an evolutionally conserved interaction between the immune and nervous systems; 3) The APOE-TREM2 pathway regulates the microglia phenotype switch in neurodegenerative diseases. Provided that recent technologies allow for readily manipulating the immune system, the findings presented herein may create new vistas for therapeutic interventions in various neurological disorders.

DOI

10.13028/M2J953

Rights and Permissions

Licensed under a Creative Commons license

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Available for download on Tuesday, October 23, 2018

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