Klara Soukup, Angela Halfmann, Marie Le Bras, Emine Sahin, Sarah Vittori, Fiona Poyer, Cornelia Schuh, Romana Luger, Birgit Niederreiter, Thomas Haider, Dagmar Stoiber, Stephan Blüml, Gernot Schabbauer, Alexey Kotlyarov, Matthias Gaestel, Thomas Felzmann, Alexander M Dohnal
Dendritic cell (DC)-mediated inflammation induced via TLRs is promoted by MAPK-activated protein kinase (MK)-2, a substrate of p38 MAPK. In this study we show an opposing role of MK2, by which it consolidates immune regulatory functions in DCs through modulation of p38, ERK1/2-MAPK, and STAT3 signaling. During primary TLR/p38 signaling, MK2 mediates the inhibition of p38 activation and positively cross-regulates ERK1/2 activity, leading to a reduction of IL-12 and IL-1α/β secretion. Consequently, MK2 impairs secondary autocrine IL-1α signaling in DCs, which further decreases the IL-1α/p38 but increases the anti-inflammatory IL-10/STAT3 signaling route...
July 15, 2015: Journal of Immunology