Reduced arthritis in MIF deficient mice is associated with reduced T cell activation: down-regulation of ERK MAP kinase phosphorylation.
Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory cytokine with many cellular targets in rheumatoid arthritis (RA). MIF has been reported to activate cells via mitogen-activated protein kinase and serine/threonine kinase (AKT or protein kinase B)-dependent signal transduction pathways. Its contribution to T cell activation and signalling in RA is not known. Using MIF -/- mice and a T cell-mediated model of RA, antigen-induced arthritis, we investigated the role of MIF in T cell activation and signalling. Arthritis severity was significantly reduced in MIF -/- mice compared with wildtype mice. This reduction was associated with decreased T cell activation parameters including footpad delayed type hypersensitivity, antigen-induced splenocyte proliferation and cytokine production. Splenocyte proliferation required extracellular signal-regulated kinase (ERK)1/2 phosphorylation, and decreased T cell activation in MIF -/- mice was associated with decreased phosphorylation of ERK1/2 but not AKT. Collectively, these data suggest that MIF promotes antigen-specific immune responses via regulation of ERK phosphorylation in T cells.
Santos
L L
LL
Monash University, Department of Medicine, Monash Medical Centre, Clayton, Melbourne, Victoria, Australia. lanie.santos@med.monash.edu.au
Dacumos
A
A
Yamana
J
J
Sharma
L
L
Morand
E F
EF
D000818:Animals; D001169:Arthritis, Experimental / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D019746:Intramolecular Oxidoreductases / Q000172:deficiency* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008263:Macrophage Migration-Inhibitory Factors / Q000172:deficiency* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D012710:Serum Albumin, Bovine / Q000276:immunology; D013585:Synovitis / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*
D016207:Cytokines; D007074:Immunoglobulin G; D008263:Macrophage Migration-Inhibitory Factors; C029180:methylated bovine serum albumin; D012710:Serum Albumin, Bovine; D048049:Extracellular Signal-Regulated MAP Kinases; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse