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dc.contributor.advisorYang, Yuhong
dc.creatorFarinas, Marissa
dc.description.abstractMultiple Sclerosis (MS) is a chronic autoimmune disorder of the central nervous system (CNS) in which the body's immune system attacks the fatty myelin sheath surrounding neurons, resulting in impaired neuronal signaling. Myelin-specific CD4 effector T cells (Teff) are pathogenic while CD4 T regulatory cells (Treg) are advantageous by suppressing Teff cells in both MS and its murine model, experimental autoimmune encephalomyelitis (EAE). Th17 cells are a major subset of Teff cells that mediate the formation of acute inflammatory CNS lesions and disease progression in EAE. Th17 cells are also implicated in MS pathogenesis. We focused on the Interleukin (IL)-6/STAT3 pathway in MS pathogenesis, as dysregulation of this pathway is observed in MS patients. IL-6 is a cytokine that signals through the transcription factor STAT3 to induce the development of Th17 cells, which produce a proinflammatory cytokine, IL-17. Moreover, IL-6 suppresses the generation of inducible Tregs (iTregs) and facilitates the Teff resistance to Treg-mediated suppression in MS patients, skewing the Teff:Treg balance towards Teff cells. This evidence suggests targeting STAT3 signaling may provide therapeutic benefit for MS. We developed a novel small molecule inhibitor, LLL12b, of STAT3. In previous studies, we found that LLL12b suppresses Th17 development and promotes iTreg development of murine and human CD4 T cells. In this study, we examined whether LLL12b could suppress the resistance of Teff cells from MS patients to Treg-mediated suppression. Using a CFSE-based suppression assay, our data show that LLL12b increases the Treg-mediated suppression on Teff cells, which may shift the functional Teff:Treg balance towards Tregs. Taken together, our novel small molecule STAT3 inhibitor may normalize the Teff:Treg balance of CD4 T cells and provide a novel therapeutic strategy for ameliorating disease progression in MS.en_US
dc.description.sponsorshipCollege of Arts and Sciences Undergraduate Research Scholarshipen_US
dc.description.sponsorshipCollege of Arts and Sciences Undergraduate Research Apprentice Program scholarshipen_US
dc.description.sponsorshipNIH funding (1R01NS088437-01A1)en_US
dc.publisherThe Ohio State Universityen_US
dc.relation.ispartofseriesThe Ohio State University. Department of Neuroscience Honors Theses; 2020en_US
dc.subjectSmall molecule inhibitoren_US
dc.subjectMultiple Sclerosisen_US
dc.subjectCD4 T cellsen_US
dc.subjectTeff:Treg balanceen_US
dc.titleNovel small molecule STAT3 inhibitor improves Teff:Treg balance of CD4 T cells from Multiple Sclerosis patientsen_US
dc.description.embargoNo embargoen_US
dc.rights.ccAttribution 4.0 International*
dc.description.academicmajorAcademic Major: Neuroscienceen_US

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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International