Reduced arthritis in MIF deficient mice is associated with reduced T cell activation: down-regulation of ERK MAP kinase phosphorylation

被引：40

作者：

Santos, L. L. ^{[1
]}

Dacumos, A. ^{[1
]}

Yamana, J. ^{[1
]}

Sharma, L. ^{[2
]}

Morand, E. F. ^{[1
]}

机构：

[1] Monash Univ, Dept Med, Monash Med Ctr, Melbourne, Vic 3168, Australia

[2] Burnett Inst, Melbourne, Vic, Australia

来源：

CLINICAL AND EXPERIMENTAL IMMUNOLOGY | 2008年 / 152卷 / 02期

关键词：

arthritis; ERK; MIF; T cell;

D O I：

10.1111/j.1365-2249.2008.03639.x

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：372 / 380

页数：9