In vivo blockade of macrophage migration inhibitory factor ameliorates acute experimental autoimmune encephalomyelitis by impairing the homing of encephalitogenic T cells to the central nervous system.
Macrophage migration inhibitory factor (MIF) is a cytokine that plays a critical role in the regulation of macrophage effector functions and T cell activation. However, its role in the pathogenesis of T cell-mediated autoimmune diseases, such as experimental autoimmune encephalomyelitis (EAE), has remained unresolved. In this study, we report that anti-MIF Ab treatment of SJL mice with acute EAE improved the disease severity and accelerated the recovery. Furthermore, the anti-MIF treatment impaired the homing of neuroantigen-reactive pathogenic T cells to the CNS in a VCAM-1-dependent fashion. Interestingly, MIF blockade also decreased the clonal size of the neuroantigen-specific Th1 cells and increased their activation threshold. Taken together, the results demonstrate an important role for MIF in the pathogenesis of EAE/multiple sclerosis and suggest that MIF blockade may be a promising new strategy for the treatment of multiple sclerosis.
Denkinger
Claudia M
CM
Institute of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Denkinger
Michael
M
Kort
Jens J
JJ
Metz
Christine
C
Forsthuber
Thomas G
TG
D000208:Acute Disease; D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007106:Immune Sera / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018991:Myelin Proteolipid Protein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D018984:Epitopes, T-Lymphocyte; D007106:Immune Sera; D008263:Macrophage Migration-Inhibitory Factors; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D019010:Vascular Cell Adhesion Molecule-1; C435023:myelin proteolipid protein (139-151)