| dc.identifier.uri | http://hdl.handle.net/11401/76522 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Dissertation | |
| dcterms.abstract | Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by progressive demyelination and degeneration of neurons. As MS progresses, T cells that are normally excluded from the CNS cross the compromised blood-brain barrier due to recruitment by the resident CNS immune cells, microglia. Both microglia and T cells can promote either disease progression or disease resolution through polarization into pro- and anti-inflammatory subsets, respectively. Therapeutic approaches in MS focus on diminishing inflammation and promoting expansion of anti-inflammatory immune cell populations. Tuftsin, a stimulator of macrophage/microglial activation, is a naturally occurring tetrapeptide with the sequence T-K-P-R. In the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, infusion of tuftsin attenuates disease symptoms and promotes the anti-inflammatory response. Tuftsin's binding target is neuropilin-1 (Nrp1), a protein with critical roles in the nervous, vascular, and immune systems. In this study, we investigated whether tuftsin's beneficial effects during EAE are mediated by Nrp1. Our results show that tuftsin polarizes microglia to an anti-inflammatory phenotype specifically via Nrp1 through the canonical TGFβ pathway. Further, we report that Nrp1 promotes long, functional contacts between microglia and immunosuppressive regulatory T cells. Mice treated with tuftsin during EAE show significant reductions in disease severity, demyelination, weight loss, and inflammatory polarization in microglia. However, in mice lacking Nrp1 on macrophages/microglia, tuftsin's beneficial effects were completely abolished. Taken together, these data indicate that the Nrp1-microglial axis is the primary mediator of tuftsin's function in vivo. The results of this project provide us a fuller understanding of the mechanism of tuftsin's action during EAE, and may lead to the development of more effective disease modifying reagents for MS treatment | |
| dcterms.available | 2017-09-20T16:50:32Z | |
| dcterms.contributor | Tsirka, Styliani-Anna E | en_US |
| dcterms.contributor | Carpino, Nicholas | en_US |
| dcterms.contributor | Colognato, Holly | en_US |
| dcterms.contributor | van der Velden, Adrianus. | en_US |
| dcterms.creator | Nissen, Jillian Cypser | |
| dcterms.dateAccepted | 2017-09-20T16:50:32Z | |
| dcterms.dateSubmitted | 2017-09-20T16:50:32Z | |
| dcterms.description | Department of Molecular and Cellular Pharmacology. | en_US |
| dcterms.extent | 174 pg. | en_US |
| dcterms.format | Monograph | |
| dcterms.format | Application/PDF | en_US |
| dcterms.identifier | http://hdl.handle.net/11401/76522 | |
| dcterms.issued | 2015-08-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2017-09-20T16:50:32Z (GMT). No. of bitstreams: 1
Nissen_grad.sunysb_0771E_11728.pdf: 26082325 bytes, checksum: 9f6c0b79177f73027429779e5733e5e5 (MD5)
Previous issue date: 2014 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Neurosciences | |
| dcterms.title | Tuftsin and its receptor neuropilin-1 in the attenuation of experimental autoimmune encephalomyelitis | |
| dcterms.type | Dissertation | |
