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Mnk1 is essential to efficient murine T cell IFNgamma release
Author(s) -
Burnette Barry Lee,
Monahan Joseph B
Publication year - 2010
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.24.1_supplement.963.7
Subject(s) - knockout mouse , immunology , inflammation , priming (agriculture) , t cell , biology , cancer research , immune system , receptor , biochemistry , botany , germination
Mnk1 is a MAPKAP kinase activated by ERK or p38 which appears to be non‐essential for normal growth or development based on the lack of any adverse phenotype in knockout mice. A role for Mnk1 has been implicated in inflammatory responses and tumorigenesis, and therefore we investigated the role of Mnk1 in the release of pro‐inflammatory mediators from T cells. We generated an Mnk1 knockout mouse on a DBA1 background, and isolated wildtype and Mnk1‐deficient splenic T cells by negative selection. T cells were stimulated with anti‐CD3 and anti‐CD28 antibodies and after 16 hours, culture supernatants were assayed by electrochemiluminescent ELISA for murine IFN‐γ, IL‐1β, IL‐2, IL‐4, IL‐5, KC, IL‐10, IL‐12, and TNF‐α. While IL‐4 and IL‐12 production were significantly suppressed in knockout T cells relative to wild type, IFN‐γ release was inhibited by greater than 80% of control. These results suggested that Mnk1 may effect IFN‐γ production from inflammatory T cells. Although IFN‐γ priming of innate effector cells may play an important role in modulating inflammatory responses and can abrogate anti‐inflammatory signaling, it also has pleiotropic effects and may ameliorate or exacerbate autoimmune diseases dependent upon condition or stage. We propose Mnk1 may be a therapeutic target for autoimmune diseases by suppressing IFN‐γ production.