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Macrophage migration inhibitory factor stimulates interleukin‐17 expression and production in lymph node cells
Author(s) -
Stojanović Ivana,
Cvjetićanin Tamara,
Lazaroski Sandra,
StošićGrujičić Stanislava,
Miljković Djordje
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2008.02879.x
Subject(s) - macrophage migration inhibitory factor , cytokine , tumor necrosis factor alpha , stat protein , biology , transforming growth factor , immunology , mapk/erk pathway , janus kinase , kinase , stat3 , signal transduction , microbiology and biotechnology
Summary Interleukin (IL)‐17 is a pro‐inflammatory cytokine produced by recently described T helper type 17 (Th17) cells, which have critical role in immunity to extracellular bacteria and the pathogenesis of several autoimmune disorders. IL‐6 and transforming growth factor (TGF)‐β are crucial for the generation of Th17 cells in mice, while the production of IL‐17 is supported by various cytokines, including IL‐23, IL‐1β, IL‐21, IL‐15 and tumour necrosis factor (TNF)‐α. In this study, the influence of a multifunctional cytokine, macrophage migration inhibitory factor (MIF), on IL‐17 production in mice was investigated. Treatment of lymph node cells (LNCs) with recombinant MIF up‐regulated mitogen‐stimulated IL‐17 expression and secretion. Additionally, LNCs from MIF knockout mice (mif −/− ) had severely impaired production of IL‐17, as well as of IL‐1β, IL‐6, IL‐23 and TGF‐β. When stimulated with recombinant IL‐1β, IL‐23 or TNF‐α, mitogen‐triggered mif −/− LNCs were fully able to achieve the IL‐17 production seen in wild‐type (WT) LNCs, while the addition of IL‐6 and TGF‐β had no effect. Finally, after injection of mice with complete Freund’s adjuvant, secretion of IL‐17 as well as the number of IL‐17‐positive cells was significantly lower in the draining lymph nodes of mif −/− mice in comparison with WT mice. The effect of MIF on IL‐17 production was dependent on p38, extracellular signal‐regulated kinase (ERK), Jun N‐terminal kinase (JNK) and Janus kinase 2/signal transducer and activator of transcription 3 (Jak2/STAT3), and not on nuclear factor (NF)‐κB and nuclear factor of activated T cells (NFAT) signalling. Bearing in mind the contribution of MIF and IL‐17 to the pathology of inflammatory and autoimmune disorders, from the results presented here it seems plausible that targeting MIF biological activity could be a valid therapeutic approach for the treatment of such diseases.