MEKK3 over-expression contributes to the hyper-responsiveness of IL-12-overproducing cells and CD4+

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  Elevated IL-12 production and higher rate of CD4+ T conventional (Tconv) cell proliferation in NOD mice have been implicated in the progression of type 1 diabetes.However, the underlying mechanisms remain largely unknown, even though enhanced activation of the IκB kinase (IKK)/NF-κB pathway has been revealed to mediate IL-12 overproduction.Here, we report that deviated p38 MAPK activation also contributes to elevated IL-12 production with a mechanism involving MAPK-activated protein kinase-2 (MK-2)-mediated stabilization of IL-12p40 mRNA.
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