Exosomes: Mediators of Pregnancy-associated Immune Modulation and Neuroprotection in a Model of Multiple Sclerosis

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Title: Exosomes: Mediators of Pregnancy-associated Immune Modulation and Neuroprotection in a Model of Multiple Sclerosis
Creators: Williams, Jessica
Advisor: Whitacre, Caroline
Issue Date: 2011-03
Abstract: Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) thought to be initiated by myelin-specific T cells. MS is characterized by inflammation and myelin damage within the CNS. MS disease relapses are markedly reduced during pregnancy, the greatest suppression in disease activity observed during the third trimester. Exosomes are small lipid-bound vesicles that function as facilitators of intercellular communication and are augmented in the serum during pregnancy. Exosomes are able to modulate cells of the immune and central nervous systems by relaying molecular signals from their cell of origin to target cells. Therefore, the goal of this study is to elucidate the role of serum exosomes in pregnancy-associated MS suppression. In a murine model of MS, experimental autoimmune encephalomyelitis (EAE), disease severity is significantly reduced when pregnancy is induced during active EAE. Interestingly, pregnancy-derived serum exosomes administered to mice with EAE reduced clinical severity following a single treatment. Further, exosomes are able to suppress the activation of myelin-specific T cells measured by a reduction in proliferation and interferon-gamma expression. We have also demonstrated that serum exosomes enhance the proliferation and maturation of oligodendrocyte precursor cells (OPC) in vitro and that migration of OPCs to CNS lesions is mediated by pregnancy-derived serum exosomes. To determine proteins expressed in pregnancy- versus control-derived exosomes, we performed differential gel electrophoresis. Proteins enriched in pregnancy exosomes facilitate the local action of corticosterone, scavenge oxygen-derived free radicals, and provide survival signals to oligodendrocytes. These data suggest that serum exosomes are critical modulators of both the immune and central nervous systems during pregnancy and govern suppression of EAE and MS. Harnessing the mechanism by which exosomes suppress immunity, enhance the function of OPCs, and consequently suppress clinical EAE, can provide valuable insight into therapy development in MS.
Embargo: No embargo
Series/Report no.: 2011 Edward F. Hayes Graduate Research Forum. 25th
Keywords: Multiple sclerosis
Description: Professional Biological Sciences: 1st Place (The Ohio State University Edward F. Hayes Graduate Research Forum)
URI: http://hdl.handle.net/1811/48335
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