MGL signaling augments TLR2‐mediated responses for enhanced IL‐10 and TNF‐α secretion. Issue 2 (6th June 2013)

• Record Type: Journal Article
• Authors: van Vliet, Sandra J.; Bay, Sylvie; Vuist, Ilona M.; Kalay, Hakan; García‐Vallejo, Juan J.; Leclerc, Claude; van Kooyk, Yvette
• Is Part Of: Journal of leukocyte biology. Volume 94:Issue 2(2013)
• Page Start: 315
• Page End: 323
• Publication Date: 2013-06-06
• Subjects: dendritic cells -- C‐type lectin -- macrophage galactose‐type lectin -- Tn antigen; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.1012520
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : The C‐type lectin MGL activates the ERK‐p90RSK‐CREB axis, which together with TLR2 signaling leads to enhanced secretion of IL‐10 and TNFα. Abstract : DCs orchestrate immune responses to infectious pathogens and disturbances in tissue integrity. Equipped with C‐type lectins, DCs can respond to environmental changes in glycosylation. Many C‐type lectins are capable of modulating TLR activation, thereby facilitating tailor‐made immune reactions. Here, we investigated the signaling properties of the C‐type lectin MGL and show that MGL engagement by agonistic antibodies or carbohydrate ligands couples to TLR signal transduction for increased IL‐10 and TNF‐α secretion by human monocyte‐derived DCs. MGL triggering especially synergized with TLR2‐induced pathways, leading to elevated IL‐10 mRNA levels and enhanced TNF‐α mRNA stability. In addition, MGL signaling promoted phosphorylation of the MAPK ERK and the transcription factor CREB. Whereas specific inhibitors of p90RSK blocked the MGL‐induced cytokine secretion, AP‐1 was not involved. Strikingly, NF‐κB was only crucial for the IL‐10 response and dispensable for TNF‐α production. Together, our results demonstrate that MGL activation of the ERK‐p90RSK‐CREB axis converges with TLR2‐induced pathways, thereby fine‐tuning the DC maturation phenotype.