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Controlled Delivery of a Glutamate Receptor Modulator to Promote Regulatory T cells and Restrain Autoimmunity

dc.contributor.advisorJewell, Christopher Men_US
dc.contributor.authorGammon, Joshua Marvinen_US
dc.date.accessioned2016-02-09T06:36:04Z
dc.date.available2016-02-09T06:36:04Z
dc.date.issued2015en_US
dc.identifierhttps://doi.org/10.13016/M2GM87
dc.identifier.urihttp://hdl.handle.net/1903/17381
dc.description.abstractAutoimmunity occurs when the immune system incorrectly recognizes and attacks self-molecules. Current therapies involve broad immunosuppressants that are not curative and leave patients immunocompromised. Dendritic cells (DCs) are a target for new therapies because DCs influence the differentiation of immune effector cells. N-Phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC), a glutamate receptor enhancer, modulates DC cytokine profiles to polarize T cells toward regulatory phenotypes (TREG ) that are protective in multiple sclerosis (MS). However, PHCCC treatment is limited by poor solubility, a short half-life, and toxicity. We hypothesized that controlled delivery of PHCCC from nanoparticles would alter DC function with reduced treatment frequency. PHCCC nanoparticles attenuated DC activation and promoted TREGs while reducing toxicity 30-fold. In mouse models of MS, these particles delayed disease and reduced severity compared to an equivalent dosing schedule of soluble drug. This outcome demonstrates controlled delivery of metabolic modulators can promote tolerance, suggesting a new route to improve autoimmune therapy.en_US
dc.language.isoenen_US
dc.titleControlled Delivery of a Glutamate Receptor Modulator to Promote Regulatory T cells and Restrain Autoimmunityen_US
dc.typeThesisen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.contributor.departmentBioengineeringen_US
dc.subject.pqcontrolledBiomedical engineeringen_US
dc.subject.pqcontrolledImmunologyen_US
dc.subject.pquncontrolledAutoimmunityen_US
dc.subject.pquncontrolledBiomaterialen_US
dc.subject.pquncontrolledImmunotherapyen_US
dc.subject.pquncontrolledMetabolismen_US
dc.subject.pquncontrolledNanoparticleen_US
dc.subject.pquncontrolledToleranceen_US


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