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Nga Le Thesis v11 Revised.pdf (14.05 MB)

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Regulation of Intestinal Epithelial Barrier and Immune Function by Activated T Cells

Le, Nga Thi Thanh
http://orcid.org/0000-0002-4926-175X
http://rave.ohiolink.edu/etdc/view?acc_num=case1599833768774075

Abstract Details

2021, Doctor of Philosophy, Case Western Reserve University, Molecular Biology and Microbiology.
Background and Aims: Communication between T cells and the intestinal epithelium is altered in many diseases, causing T cell activation, depletion, or recruitment and disruption of the epithelium. We hypothesize that activation of T cells regulates epithelial barrier function by targeting the assembly of the tight junction complex. Methods: In a 3-dimensional and 2-dimensional co-culture model of activated T cells subjacent to the basolateral surface of an epithelial monolayer, the pore, leak, and unrestricted pathways were evaluated using transepithelial resistance and flux of fluorescently-labelled tracers. T cells were acutely and chronically activated by cross-linking the TCR. Tight junction assembly and expression were measured using qPCR, immunoblot, and immunofluorescence confocal microscopy. Results: Co-culture with acutely and chronically activated T cells decreased the magnitude of ion flux through the pore pathway, which was maintained in the presence of acutely-activated T cells. Chronically activated T cells after 30 h induced a precipitous increase in the magnitude of both ion and molecular flux, resulting in an increase in the unrestricted pathway, destruction of microvilli, expansion in cell surface area, and cell death. These fluctuations in permeability were due to changes in the assembly and expression of tight junction proteins, cell morphology, and viability. Co-culture modulated the expression of immune mediators in the epithelium and T cells. Conclusion: Bi-directional communication between T cells and epithelium mediates a bi-phasic response in barrier integrity that is facilitated by the balance between structural proteins partitioning in the mobile lateral phase versus the tight junction complex and cell morphology.
John Tilton (Committee Chair)
Henry Boom (Committee Member)
Donald Anthony (Committee Member)
Jerrold Turner (Committee Member)
Alan Levine (Advisor)
87 p.
Biomedical Research
claudin, occludin, paracellular permeability, pore pathway, leak pathway

Recommended Citations

Citations

  • Le, N. T. T. (2021). Regulation of Intestinal Epithelial Barrier and Immune Function by Activated T Cells [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1599833768774075

    APA Style (7th edition)

  • Le, Nga. Regulation of Intestinal Epithelial Barrier and Immune Function by Activated T Cells. 2021. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1599833768774075.

    MLA Style (8th edition)

  • Le, Nga. "Regulation of Intestinal Epithelial Barrier and Immune Function by Activated T Cells." Doctoral dissertation, Case Western Reserve University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1599833768774075

    Chicago Manual of Style (17th edition)

case1599833768774075
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© 2021, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.