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Anatomic plasticity and functional impacts of neural – immune and neural – epithelial signaling in the intestine

dc.contributor.authorSchwerdtfeger, Luke A., author
dc.contributor.authorTobet, Stuart A., advisor
dc.contributor.authorChicco, Adam, committee member
dc.contributor.authorMyers, Brent, committee member
dc.contributor.authorRyan, Elizabeth, committee member
dc.date.accessioned2021-09-06T10:26:00Z
dc.date.available2022-09-03T10:26:00Z
dc.date.issued2021
dc.description2021 Summer.
dc.descriptionIncludes bibliographical references.
dc.description.abstractThe intestinal wall is a multicompartmental barrier tissue composed of over 25 distinct cell types with integrated and complex signaling both within and between compartments. The gut wall is also a large endocrine organ comprised of cells capable of producing dozens of peptides used for hormonal and other signaling functions. However, the mechanistic roles that neural secretions play in regulating the gut epithelial barrier in health and disease are not well known. Additionally, frequently used models available for studying intestinal function outside of the body lack the complexity to investigate neural – epithelial and neural – immune signaling interactions. Using a bifurcated approach to method development, we created two culture systems for maintaining the full thickness of the intestinal wall ex vivo. One method allows for culture of mouse or human organotypic intestinal slices that maintain the gut wall for 6 or 4 days, respectively. This system does not however, maintain a true luminal – epithelial barrier as seen in the in vivo gut. The second method, a microfluidic organotypic device (MOD) enables maintenance of explanted mouse or pig intestinal tissue for up to 3 days ex vivo, with an intestinal barrier intact. These two methods allow for investigating and cross-validating of numerous biological questions now previously possible using traditional culture models. Neuronal fiber proximity to gut epithelia has been shown, with goblet, tuft and enteroendocrine cells being closely opposed by fibers. Goblet cells secrete mucopolysaccharides, a first line of defense separating luminal microbiota from host tissue. I have recently shown that vasoactive intestinal peptide (VIP) can regulate goblet cell production in organotypic slices of mouse ileum. This peptide is also in close proximity to Paneth cells in the base of the crypt, and enteric mast cells. There were sex differences in baseline mast cell neuronal proximity, quantities, and cell size in mouse ileum. Further, mast cells showed a sex difference in responses to lipopolysaccharide challenge. Further investigation of neurosecretory factor regulation of immune and epithelial function is needed, both in goblet cells and other secretory epithelia like anti-microbial producing Paneth cells, and in immune components like mast cells. Graphical illustration of the dissertation project is included below.
dc.format.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.identifierSchwerdtfeger_colostate_0053A_16652.pdf
dc.identifier.urihttps://hdl.handle.net/10217/233798
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2020-
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.subjectgut
dc.subjectmast cell
dc.subjectneuroimmune
dc.subjectintestine
dc.subjectgoblet cell
dc.subjectneuroepithelial
dc.titleAnatomic plasticity and functional impacts of neural – immune and neural – epithelial signaling in the intestine
dc.typeText
dcterms.embargo.expires2022-09-03
dcterms.embargo.terms2022-09-03
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineBiomedical Sciences
thesis.degree.grantorColorado State University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)

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