Crowe, Christopher R
(2009)
Critical Role of Interleukin-17 Receptor Signaling in the Immunopathology of Influenza Infection.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Interleukin-17 (IL-17) is a cytokine produced mainly by T cell lineages that plays a keyrole in regulation of neutrophil responses. Given the importance of neutrophils in the immune response directed against extracellular pathogens, it is no surprise that IL-17 is important in host defense against a multitude of pathogens. Importantly, however, neutrophils also have been shown to play a role in several immunopathological conditions, including acute lung injury. In this dissertation, we evaluate the role that IL-17 plays in the immunopathology of influenza infection. We show here that IL-17 is produced as early as day 2 following influenza challenge, and that this expression is sustained throughout the first week of infection. Further, we identify γδ T cells as at least one important source of IL-17 in response to influenza. We also demonstrate that loss of IL-17 receptor A (IL-17RA) signaling results in a profound decrease in neutrophil recruitment to the lung following influenza challenge. This decrease in neutrophils results in substantially less inflammation and lung injury, as well as higher survival rates. Additionally, there is only a moderate impact on viral clearance and T cell responses. Further, we detail similar findings in a non-infectious aspiration model of acute lung injury. Taken together, this data suggests that IL-17 signaling may be a key event, and intriguing therapeutic target, in the pathogenesis of acute lung injury.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Crowe, Christopher R | crc21@pitt.edu | CRC21 | |
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| ETD Committee: |
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| Date: |
10 August 2009 |
| Date Type: |
Completion |
| Defense Date: |
13 May 2009 |
| Approval Date: |
10 August 2009 |
| Submission Date: |
6 August 2009 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Immunology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
immunopathology; lung immunology; neutrophils; influenza; interleukin-17 |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-08062009-211958/, etd-08062009-211958 |
| Date Deposited: |
10 Nov 2011 19:57 |
| Last Modified: |
19 Dec 2016 14:37 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/8948 |
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