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The Effect of IL-17A on Dendritic Cells

Buckingham, Catherine M.
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1307126377

Abstract Details

2011, MS, University of Cincinnati, Medicine: Immunology.
Asthma is a chronic inflammatory disorder of the airways classically thought to result from an excessive Th2-dominated immune response to inhaled environmental antigens such as house dust mite (HDM). Recently though, the observation that individuals with severe asthma express high levels of IL-17A and IL-17F suggests that Th17 cytokines may play a role in more severe disease. In support of this, we have found that A/J mice, which develop severe AHR, mount a mixed Th2/Th17 response following HDM inhalation, while C3H/HeJ mice, which develop mild AHR, mount an exclusively Th2-biased immune response. Supporting a role for IL-17A, blockade of IL-17A in A/J mice diminished AHR, while exposure of C3H/HeJ to HDM+IL-17A exacerbated disease. In preliminary studies that form the basis of this thesis, we found that IL-17A plays different roles at different phases of the allergic response. Specifically, if present at challenge, IL-17A enhances IL-13 driven signaling while the presence of IL-17A at allergen sensitization regulates the number of Tregs present in the lung following allergen exposure. However, the mechanism by which IL-17A induces negative effects on Tregs is unknown. As DCs are critical players in initiating the immune response at allergen sensitization by activating T cells and influencing their development and differentiation, we hypothesized that this impact on Tregs may be due to IL-17A mediated effects on DCs. Indeed, treatment with IL-17A after HDM exposure enhanced DC antigen uptake, MHCII and PD-L2 surface expression, and production of inflammatory cytokines known to antagonize Tregs (IL-6, TNFa). Additionally, IL-17A significantly reduced levels of IL-10, an important immunosuppressive cytokine recently associated with inhibition of the Th17-promoting cytokine, IL-23. These data suggest that the presence of IL-17A during allergen sensitization may set up a positive feedback loop that further promotes Th17-driven immune responses but impairs Tregs leading to the development of severe asthma. Further understanding the mechanisms that initiate a mixed Th2/Th17 phenotype in response to allergens should inform the development of improved therapies for severe asthma.
Marsha Wills-Karp, PhD (Committee Chair)
Edith Janssen, PhD (Committee Member)
Yui-Hsi Wang, PhD (Committee Member)
Nives Zimmermann, PhD (Committee Member)
88 p.
Immunology

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Citations

  • Buckingham, C. M. (2011). The Effect of IL-17A on Dendritic Cells [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1307126377

    APA Style (7th edition)

  • Buckingham, Catherine. The Effect of IL-17A on Dendritic Cells. 2011. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1307126377.

    MLA Style (8th edition)

  • Buckingham, Catherine. "The Effect of IL-17A on Dendritic Cells." Master's thesis, University of Cincinnati, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1307126377

    Chicago Manual of Style (17th edition)

ucin1307126377
404
© 2011, some rights reserved.Creative Commons License The Effect of IL-17A on Dendritic Cells by Catherine M. Buckingham is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by University of Cincinnati and OhioLINK.