Neuroimmune connections in the spleen : a first look at spleen glia
Abstract/Contents
- Abstract
- Non-myelinating Schwann cells (NMSCs) are the most abundant cells in the peripheral nervous system. These cells ensheath the unmyelinated autonomic nerves innervating every visceral organ. However, outside of the enteric nervous system, very little is known about what they do. Glia are best studied in the brain, can support neurons, and also modulate neuronal signaling and inflammation. In the peripheral nervous system, neuronal signaling itself may be a key immune modulator as immune organs are sympathetically innervated and stress modulates immune responses. Increased sympathetic signaling after stressful events results in profound changes in the spleen, the largest secondary lymphoid (immune) organ. For example, after a large stroke, sympathetic signaling within the spleen increases and leads to the death of B-cell populations. This thesis advances our knowledge of non-myelinating Schwann cells in the spleen (spleen glia), and how sympathetic innervation of the spleen may modulate inflammation. Chapter 1 provides an overview of what is known about the roles of the spleen and our sympathetic nervous system in inflammation. Moreover, we discuss what is known about how responses between the two systems are coordinated and what the possible key mechanisms are, particularly the importance of the splenic nerve. We also explore the role of glia in both the CNS, ENS, and PNS and mechanisms by which they alter neurotransmission and immunity. Chapter 2 contains a detailed immunohistochemical and transcriptomic characterization of spleen glia. Here I utilize immunohistochemistry to provide the first in-depth characterization of the cells. This analysis reveals the expression of two common glial markers (GFAP and S100B), a close association with sympathetic nerves, vasculature, and immune cells, as well as the density and location of the cells throughout the organ. I combine this with RNA-sequencing to further characterize spleen glia. I report that they express a host of glial genes, genes involved in neurotransmission as well as genes involved in immune responses. Lastly, I use the sequencing to provide a transcriptomic comparison of spleen glia to brain glia and enteric glia, determining that spleen glia are unique when compared to these different populations. In Chapter 3, I explore the relationship of spleen glia to the splenic nerve which they ensheath. Here, I utilize SARM1 knockout animals that are protected against Wallerian degeneration after nerve injury. The work here reveals robust physical changes to spleen glia indicating potential trophic factors involved in maintaining this relationship. Chapter 4 provides a summary of the findings reported in this dissertation and describes future studies. In total, this dissertation provides a deeper context to neuroimmune interactions in the spleen and the first characterization of a novel cell type, spleen glia.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Lucas, Tawaun Autry |
|---|---|
| Degree supervisor | Ricci, Anthony |
| Thesis advisor | Ricci, Anthony |
| Thesis advisor | Andreasson, Katrin |
| Thesis advisor | Idoyaga, Juliana |
| Thesis advisor | Talbot, William S |
| Degree committee member | Andreasson, Katrin |
| Degree committee member | Idoyaga, Juliana |
| Degree committee member | Talbot, William S |
| Associated with | Stanford University, Neurosciences Program |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Tawaun Autry Lucas. |
|---|---|
| Note | Submitted to the Neurosciences Program. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/sh607bz8649 |
Access conditions
- Copyright
- © 2021 by Tawaun Autry Lucas
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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