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.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-03242017-090325 |
| Date | 10 April 2017 |
| Creators | Bloodworth, Melissa Harintho |
| Contributors | David M. Aronoff, MD, Ray Stokes Peebles Jr., MD, Wonder Drake, MD, Joshua P. Fessel, MD, PhD, Amy S. Major, PhD, John V. Williams |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-03242017-090325/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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