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A cytokine known as MIF or GIF undergoes posttranslational modification and suppresses CD4 cell‐dependent immune responses
Author(s) -
Kim Mijwa,
Janssen Edith,
Black Roy A,
Sugie Katsuji
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1070.9
Subject(s) - cytokine , chemistry , immune system , antibody , proinflammatory cytokine , il 2 receptor , chemokine , immunoglobulin e , cxc chemokine receptors , t cell , microbiology and biotechnology , immunology , inflammation , biology , chemokine receptor
MIF is believed to be a key proinflammatory cytokine that activates the innate immunity. CD74/CD44, CXCR2 and CXCR4 have been reported to be MIF receptors. However, recombinant MIF demonstrates no cytokine activity when contaminating LPS is rigorously removed. The susceptibility of MIF−/− mice to endotoxin shock varies among reports. Here we show that this cytokine, posttranslationally modified and secreted from CD4 cells, suppresses Th effector generation. The MIF protein was also designated GIF. GIF/MIF−/− mice showed augmented T‐dependent antibody formation, especially of IgE isotype, and germinal center reactions although T‐independent antibody formation was normal. GIF−/− mice demonstrated enhanced allergic airway inflammation. More IL‐4‐ and IFN‐γ‐secreting CD4 cells were detected in GIF−/− than +/+ mice after Ova immunization. GIF−/− dendritic cells and macrophages exhibited normal antigen‐presenting capacity and responsiveness to TLR ligands. However, GIF−/− CD4 cells produced enhanced amounts of IL‐4 in vitro. GIF undergoes cysteinylation at C60 in the course of secretion. CD25‐CD4+ cells were the major source of cysteinylated GIF. rGIF modified at C60 inhibited IL‐4 production in vitro, whereas unmodified GIF had no effect. Thus non‐Treg CD4 cells posttranslationally modify and secrete this cytokine as a negative feedback of Th differentiation. Supported by NIH RO1 AI56211.