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Zepp Thesis 062514 b.pdf (2.92 MB)

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The Regulatory Roles Of Traf4 Il-17 Receptor Mediated Signaling And Disease Pathology

Zepp, Jarod A
http://rave.ohiolink.edu/etdc/view?acc_num=case1404661323

Abstract Details

2014, Doctor of Philosophy, Case Western Reserve University, Molecular Medicine.
The IL-17 cytokine family members, IL-17 and IL-25, have both been implicated in the pathogenesis of numerous inflammatory disorders including multiple sclerosis and asthma. Although IL-17 and IL-25 belong to the same cytokine family, they induce distinct gene transcriptional programs that drive contrasting physiological responses. For instance, administration of IL-17 to the lungs of mice drives the accumulation of neutrophils whereas IL-25 mediates the recruitment of eosinophils. We have shown that binding of IL-17 and IL-25 to their respective receptors leads to the recruitment of the adaptor protein ACT1 and subsequent activation of TNF-receptor associated factor (TRAF) molecules. Although numerous factors have been identified downstream of IL-17, the IL-25 pathway and factors that distinguish it from IL-17, remain obscure. Here, we tested the role of TRAF4 in the IL-17 and IL-25 pathways. In the IL-17 pathway, TRAF4 interacts with the TRAF-binding domains in ACT1 and TRAF4-deficiency enhances IL-17-induced ACT1-dependent recruitment of TRAF6 and subsequent NFkB activation. Moreover, TRAF4-deficient mice are more susceptible to IL-17-driven disease pathogenesis in a mouse model of multiple sclerosis. In contrast, we find that TRAF4 deficiency alters the IL-25 response. Together these findings implicate TRAF4 as a crucial regulatory molecule in both IL-17 and IL-25 signaling pathways.
Xiaoxia Li (Advisor)
Serpil Erzurum (Committee Member)
Timothy Nilsen (Committee Chair)
Paul Fox (Committee Member)
Olga Stenina-Adognravi (Committee Member)
155 p.
Biology
Interleukin

Recommended Citations

Citations

  • Zepp, J. A. (2014). The Regulatory Roles Of Traf4 Il-17 Receptor Mediated Signaling And Disease Pathology [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1404661323

    APA Style (7th edition)

  • Zepp, Jarod. The Regulatory Roles Of Traf4 Il-17 Receptor Mediated Signaling And Disease Pathology. 2014. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1404661323.

    MLA Style (8th edition)

  • Zepp, Jarod. "The Regulatory Roles Of Traf4 Il-17 Receptor Mediated Signaling And Disease Pathology." Doctoral dissertation, Case Western Reserve University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=case1404661323

    Chicago Manual of Style (17th edition)

case1404661323
625
© 2014, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.