NDLI: Macrophage migration inhibitory factor potentiates autoimmune-mediated neuroinflammation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Shawler, Todd Guan, Zhen Popovich, Phillip G. Whitacre, Caroline C. Satoskar, Abhay R. Williams, Jessica L. Kithcart, Aaron P. Pitt, David Cox, Gina Mavrikis Dagia, Nilesh M. Alexander, Jessica
Description	Author Affiliation: Cox GM ( Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210)
Abstract	Macrophage migration inhibitory factor (MIF) is a multipotent cytokine that is associated with clinical worsening and relapses in multiple sclerosis (MS) patients. The mechanism through which MIF promotes MS progression remains undefined. In this study, we identify a critical role for MIF in regulating CNS effector mechanisms necessary for the development of inflammatory pathology in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Despite the ability to generate pathogenic myelin-specific immune responses peripherally, MIF-deficient mice have reduced EAE severity and exhibit less CNS inflammatory pathology, with a greater percentage of resting microglia and fewer infiltrating inflammatory macrophages. We demonstrate that MIF is essential for promoting microglial activation and production of the innate soluble mediators IL-1ß, IL-6, TNF- , and inducible NO synthase. We propose a novel role for MIF in inducing microglial C/EBP-ß, a transcription factor shown to regulate myeloid cell function and play an important role in neuroinflammation. Intraspinal stereotaxic microinjection of MIF resulted in upregulation of inflammatory mediators in microglia, which was sufficient to restore EAE-mediated inflammatory pathology in MIF-deficient mice. To further implicate a role for MIF, we show that MIF is highly expressed in human active MS lesions. Thus, these results illustrate the ability of MIF to influence the CNS cellular and molecular inflammatory milieu during EAE and point to the therapeutic potential of targeting MIF in MS.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	3
Volume Number	191
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2013-08-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Central Nervous System Immunology Encephalomyelitis, Autoimmune, Experimental Intramolecular Oxidoreductases Physiology Macrophage Migration-inhibitory Factors Microglia Metabolism Animals Ccaat-enhancer-binding Protein-beta Biosynthesis Inflammation Interleukin-1beta Interleukin-6 Deficiency Genetics Macrophages Mice Mice, Inbred C57bl Mice, Knockout Multiple Sclerosis Nitric Oxide Synthase Type Ii Tumor Necrosis Factor-alpha Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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