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The Influence of Interleukin 21 and T Follicular Helper Cells in Hypertension and Vascular Dysfunction

dc.creatorDale, Bethany Lyn
dc.date.accessioned2020-08-24T11:49:50Z
dc.date.available2020-04-30
dc.date.issued2019-04-30
dc.identifier.urihttps://etd.library.vanderbilt.edu/etd-04252019-201237
dc.identifier.urihttp://hdl.handle.net/1803/15413
dc.description.abstractThe role of T and B cells of the adaptive immune have been implicated in hypertension, but the mechanisms by which they produce a coordinated response is unknown. T follicular helper (Tfh) cells that produce interleukin 21 (IL- 21), can act upstream of IL-17A and interferon gamma (IFNg) which are known to promote hypertension, as well as promote germinal center (GC) B cell responses leading to immunoglobulin (Ig) production. The role of IL-21 and Tfh cells were investigated using two mouse models, Il21-/- mice, and Bcl6flox/floxTgCD4cre mice, as well as pharmacological intervention after the onset of hypertension using therapeutic grade neutralizing antibodies to murine IL-21. The impact genetic mouse lines or therapeutic intervention had on hypertension and end-organ damage were assessed by blood pressure measurements, vascular reactivity studies, vascular inflammation, and aortic remodeling. The results of these studies were associated with hypertension in humans through measurement of T cell production of IL-21 and IL-17A from peripheral blood. Additionally, through the use of mass cytometry and cytometry by time of flight (CyTOF), the ability to identify and detect previously unknown producing cells of IL-17A and INFg was accomplished.
dc.format.mimetypeapplication/pdf
dc.subjecthypertension
dc.subjectvascular dysfunction
dc.subjectinterleukin 21
dc.subjectT follicular helper
dc.subjectblood pressure
dc.titleThe Influence of Interleukin 21 and T Follicular Helper Cells in Hypertension and Vascular Dysfunction
dc.typedissertation
dc.contributor.committeeMemberJeffrey Rathmell
dc.contributor.committeeMemberRaymond Harris
dc.contributor.committeeMemberAmbra Pozzi
dc.contributor.committeeMemberJonathan Irish
dc.type.materialtext
thesis.degree.namePHD
thesis.degree.leveldissertation
thesis.degree.disciplineMolecular Physiology and Biophysics
thesis.degree.grantorVanderbilt University
local.embargo.terms2020-04-30
local.embargo.lift2020-04-30
dc.contributor.committeeChairAlyssa Hasty


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