A Systems Approach to Dissecting Immune Gene Regulatory Networks in the Modulation of Brain Function
Authors
Xu, YangFaculty Advisor
Vladimir LitvakAcademic Program
Interdisciplinary Graduate ProgramUMass Chan Affiliations
Microbiology and Physiological SystemsDocument Type
Doctoral DissertationPublication Date
2017-10-20Keywords
NeuroimmunologyT cells
social behavior
Microglia
Neurodegenerative disease
Rett syndrome
Systems biology
Bioinformatics
Biology
Neuroscience and Neurobiology
Systems Biology
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Show full item recordAbstract
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/M2J953Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32306Rights
Licensed under a Creative Commons licenseDistribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.13028/M2J953
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