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Critical Role of Interleukin-17 Receptor Signaling in the Immunopathology of Influenza Infection

Crowe, Christopher R (2009) Critical Role of Interleukin-17 Receptor Signaling in the Immunopathology of Influenza Infection. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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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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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Crowe, Christopher Rcrc21@pitt.eduCRC21
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairKolls, Jayjay.kolls@chp.eduJKK23
Committee MemberGambotto, Andreaagamb@pitt.eduAGAMB
Committee MemberNau, Gerardgjnau@mgb.pitt.eduGJNAU
Committee MemberRay, Prabirrayp@pitt.eduRAYP
Committee MemberRoss, Tedtmr15@pitt.eduTMR15
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:, etd-08062009-211958
Date Deposited: 10 Nov 2011 19:57
Last Modified: 19 Dec 2016 14:37


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