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Title page for ETD etd-03242017-090325


Type of Document Dissertation
Author Bloodworth, Melissa Harintho
Author's Email Address melissa.h.bloodworth@vanderbilt.edu
URN etd-03242017-090325
Title Regulation of Immune Responses during Airway Inflammation
Degree PhD
Department Microbiology and Immunology
Advisory Committee
Advisor Name Title
David M. Aronoff, MD Committee Chair
Amy S. Major, PhD Committee Member
John V. Williams Committee Member
Joshua P. Fessel, MD, PhD Committee Member
Ray Stokes Peebles Jr., MD Committee Member
Wonder Drake, MD Committee Member
Keywords
  • type 2 immunity (Th2)
  • gamma-delta 17 (γδ17) cells
  • STAT6
  • Klebsiella pneumoniae
  • glucagon-like peptide 1 (GLP-1)
  • respiratory syncytial virus (RSV)
  • phenome-wide association study (PheWAS)
  • regulatory T cells (Tregs)
  • prostacyclin (PGI2)
Date of Defense 2017-03-13
Availability unrestricted
Abstract
Allergic asthma is refractory to corticosteroid treatment in up to 10% of patients and often leads to hospital admissions caused by respiratory viral and/ or bacterial infections. In these studies, I found that: 1) STAT6 inhibited innate γδ17 cell immune responses. STAT6 suppression of γδ17 cell function may provide one explanation for why asthmatic patients have significantly greater risk for invasive bacterial disease, including pneumonia, than nonasthmatic subjects. 2) A GLP-1R agonist, an FDA-approved agent currently used for Type II Diabetes, attenuated the type 2 immune response to RSV and attenuates RSV illness. The current availability of GLP-1R agonists for human treatment highlights the clinical significance of these studies as this therapy could be immediately transferrable to RSV disease. 3) PGI2, an FDA-approved agent currently used for pulmonary hypertension, protected against autoimmunity; enhanced Treg stability and function; rendered T effector cells more susceptible to Treg- mediated suppression; and promoted iTreg differentiation. PGI2 may therefore represent a novel treatment strategy for diseases that result from Treg dysregulation.
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