Ramani, Kritika
(2017)
Regulation of renal immunity and immunopathology by interleukin-17.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Pro-inflammatory cytokine IL-17 has been implicated in tissue damage associated with various autoimmune diseases. IL-17 is also known to contribute in immunity against bacterial and fungal pathogens. Most research over the past decade focused on understanding how IL-17- producing cells are generated, but far less is known about the organ specific responses of IL-17. In this thesis, we delineate the specific roles for IL-17 in the kidney, an organ susceptible to both auto-inflammatory conditions and infection. With the help of murine models, we outline the IL-17-driven responses in infection and autoimmunity. We studied the role for IL-17 mediated protection in disseminated candidiasis, a fatal nosocomial infection associated with high mortality. We discovered a previously unappreciated connection between IL-17 and the kallikrein- kinin system in renal protection against disseminated candidiasis. Simultaneously, we defined the cellular and molecular events in IL-17 driven renal tissue damage in murine models of autoimmune glomerulonephritis and lupus nephritis. Our results suggest that the kidney specific role of IL-17 is in the regulation of innate immune cells associated with kidney pathology. In addition, we were the first to show that neutralization of IL-17 ameliorated renal pathology in the autoimmune glomerulonephritis model. The consequence of unchecked renal inflammation is irreversible damage in the kidney, leading to fibrosis. In the case of inflammation mediated end organ fibrosis, the role for pro-fibrotic or anti-fibrotic role for IL-17 is debatable. We focused our attention on the role for IL-17-mediates immune responses in the kidney in a mouse model of fibrosis. We uncovered a surprisingly protective, anti-fibrotic role for IL-17 in the kidney that was driven by the IL-17-Klk1 axis. In summary, our findings have advanced the understanding of IL-17 mediated immunity and immunopathology and opens up the potential to develop therapeutic strategies based on the context of the disease.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
| Title | Member | Email Address | Pitt Username | ORCID |
|---|
| Thesis Advisor | Biswas, Partha | psb13@pitt.edu | | |
|
| Date: |
18 January 2017 |
| Date Type: |
Publication |
| Defense Date: |
9 November 2016 |
| Approval Date: |
18 January 2017 |
| Submission Date: |
8 December 2016 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
190 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Immunology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Interleukin-17, disseminated candidiasis, autoimmune glomerulonephritis, renal fibrosis, C.albicans, kidney |
| Date Deposited: |
18 Jan 2017 15:46 |
| Last Modified: |
18 Jan 2019 06:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/30517 |
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