Macrophage migration inhibitory factor: a study of the effects on the central nervous system microenvironment in experimental autoimmune encephalomyelitis
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The Ohio State University / OhioLINK
2011
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=osu1322606234 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-osu13226062342021-08-03T06:04:18Z Macrophage migration inhibitory factor: a study of the effects on the central nervous system microenvironment in experimental autoimmune encephalomyelitis Cox, Gina Mavrikis Biomedical Research Immunology macrophage migration inhibitory factor multiple sclerosis experimental autoimmune encephalomyelitis Multiple Sclerosis (MS) is a progressive immune-mediated demyelinating disease of the central nervous system (CNS). Over time, permanent neurological disability accumulates as a result of the chronic activation of inflammatory and neurodegenerative pathways within the CNS. Macrophage migration inhibitory factor (MIF) is a multipotent cytokine that has recently been associated with clinical worsening and relapses in MS. The mechanism by which MIF promotes MS progression remains undefined. In an animal model of MS, experimental autoimmune encephalomyelitis (EAE), we identify a critical role for MIF in regulating CNS effector mechanisms necessary for the development of inflammatory pathology. Despite the ability to generate pathogenic myelin-specific immune responses peripherally, MIF-deficient mice have reduced EAE severity and exhibit less CNS inflammatory pathology. MIF-deficiency appears to mediate host protection from chronic EAE at the level of the CNS, since MIF-deficient mice exhibit significantly less disease following transfer of pathogenic myelin-specific cells. Upon examination of MS brain tissue, we found that MIF is highly expressed in regions of active inflammation, suggesting that MIF may have profound influence on the CNS inflammatory response. These studies highlight the ability of MIF to promote the activation and recruitment of CNS macrophages during EAE: both CNS effector mechanisms critical for EAE progression. MIF exerts potent proinflammatory effects on microglia and polarizes a proinflammatory gene expression profile associated with CNS autoimmune-mediated tissue damage. We propose a novel role for MIF in regulating the transcriptional activity of key mediators of myeloid cell function, including C/EBP-β, a transcription factor previously implicated in neuroinflammation. Lastly, we used intraspinal stereotaxic microinjection to examine the site-specific activity of MIF in the specialized CNS microenvironment. Intraspinal microinjection of MIF fully reconstitutes the ability of MIF-deficient mice to develop autoimmune-mediated inflammatory pathology, suggesting that MIF creates a CNS microenvironment permissive to the development of neuroinflammation. Collectively, these data demonstrate the ability of MIF to influence the CNS cellular and molecular inflammatory milieu in EAE and suggests that targeting MIF may represent a novel therapeutic approach for resolving CNS inflammation in MS. 2011-12-19 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1322606234 http://rave.ohiolink.edu/etdc/view?acc_num=osu1322606234 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Biomedical Research Immunology macrophage migration inhibitory factor multiple sclerosis experimental autoimmune encephalomyelitis |
| spellingShingle |
Biomedical Research Immunology macrophage migration inhibitory factor multiple sclerosis experimental autoimmune encephalomyelitis Cox, Gina Mavrikis Macrophage migration inhibitory factor: a study of the effects on the central nervous system microenvironment in experimental autoimmune encephalomyelitis |
| author |
Cox, Gina Mavrikis |
| author_facet |
Cox, Gina Mavrikis |
| author_sort |
Cox, Gina Mavrikis |
| title |
Macrophage migration inhibitory factor: a study of the effects on the central nervous system microenvironment in experimental autoimmune encephalomyelitis |
| title_short |
Macrophage migration inhibitory factor: a study of the effects on the central nervous system microenvironment in experimental autoimmune encephalomyelitis |
| title_full |
Macrophage migration inhibitory factor: a study of the effects on the central nervous system microenvironment in experimental autoimmune encephalomyelitis |
| title_fullStr |
Macrophage migration inhibitory factor: a study of the effects on the central nervous system microenvironment in experimental autoimmune encephalomyelitis |
| title_full_unstemmed |
Macrophage migration inhibitory factor: a study of the effects on the central nervous system microenvironment in experimental autoimmune encephalomyelitis |
| title_sort |
macrophage migration inhibitory factor: a study of the effects on the central nervous system microenvironment in experimental autoimmune encephalomyelitis |
| publisher |
The Ohio State University / OhioLINK |
| publishDate |
2011 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=osu1322606234 |
| work_keys_str_mv |
AT coxginamavrikis macrophagemigrationinhibitoryfactorastudyoftheeffectsonthecentralnervoussystemmicroenvironmentinexperimentalautoimmuneencephalomyelitis |
| _version_ |
1719430368778518528 |