First Advisor

DeKrey, Gregory

First Committee Member

Pulen, Nicholas A.

Second Committee Member

Thomas, Mark P.

Third Committee Member

Hydock, David

Degree Name

Doctor of Philosophy

Document Type

Dissertation

Date Created

5-2025

Department

College of Natural and Health Sciences, Biological Sciences, Biological Sciences Student Work

Abstract

Previous studies conducted in our laboratory suggest that activation of the aryl hydrocarbon receptor (AhR) activation with the prototypical ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) initially suppresses both fecal and serum antigen-specific IgA responses, but fecal antigen-specific IgA levels recover from suppression while serum IgA levels do not. The purpose of the research detailed in this dissertation was to explore two potential mechanisms allowing for the more rapid recovery of antigen-specific IgA in the feces relative to the serum: (1) an increase in myeloid-derived suppressor cells (MDSCs) that enhance IgA antibody responses in intestinal tissues, and (2) an increase in the migration of antibody-secreting B cells to the intestines. Additionally, this research aimed to determine if sex plays a role in the differential regulation of IgA responses we have observed. We used a model in which mice were treated with vehicle (peanut oil) or TCDD and then orally immunized with cholera toxin (CT) to create a robust antigen-specific IgA response. In our sex-based studies, CT-specific IgA levels in the feces and serum of both male (n = 25) and female (n = 15) mice were determined by enzyme-linked immunosorbent assay (ELISA). We found that males and females are differentially impacted by TCDD treatment. In females, fecal CT-specific IgA levels recover from suppression within 3 weeks of treatment, while IgA levels in male mice do not recover by that time. To examine the effect of TCDD treatment on the number of MDSCs, we used the same treatment and immunization model as previously described in female mice only (n = 32 per treatment group). The number of MDSCs present in both gut-associated and blood-associated lymphoid tissues was determined by flow cytometry. We found that TCDD treatment significantly increased the number of MDSCs in the Peyer’s patches, but did not alter the number of MDSCs in the spleen, mesenteric lymph nodes, or small intestinal lamina propria. To examine the effect of TCDD treatment on B cell migration, we determined the number of B cells present in spleen, bone marrow, and lamina propria of control and TCDD-treated mice. Female mice (n = 36 per treatment group) were treated using the same treatment and immunization model as previously described. The number of B cells in each tissue was determined by flow cytometry. We observed no significant differences in the number or percentage of CD19+ or IgA+ B cells in any tissue examined. Together, these findings indicate that MDSCs play a role in regulating fecal CT-specific in our model. While our B cell data do not directly support our hypothesis that TCDD treatment enhances B cell migration to the gut, they are consistent with our previous findings.

Abstract Format

html

Language

English

Places

Greeley, Colorado

Extent

153 pages

Local Identifiers

King2_unco_0161D_11327.pdf

Rights Statement

Copyright is held by the author.

Digital Origin

Born digital

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