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dc.contributor.authorHupfer, Thomas
dc.contributor.authorSchick, Judith
dc.contributor.authorJozefowski, Katrin
dc.contributor.authorVoehringer, David
dc.contributor.authorOstrop, Jenny
dc.contributor.authorLang, Roland
dc.description.abstractThe C-type lectin receptors (CLRs) Mincle, Mcl, and Dectin-2 bind mycobacterial and fungal cell wall glycolipids and carbohydrates. Recently, we described that expression of these CLR is downregulated during differentiation of human monocytes to dendritic cells (DC) in the presence of GM-CSF and IL-4. Here, we demonstrate that the Th2 cytokine IL-4 specifically inhibits expression of Mincle, Mcl, and Dectin-2 in human antigen-presenting cells (APC). This inhibitory effect of IL-4 was observed across species, as murine macrophages and DC treated with IL-4 also downregulated these receptors. IL-4 blocked upregulation of Mincle and Mcl mRNA expression and cell surface protein by murine macrophages in response to the Mincle ligand Trehalose-6,6-dibehenate (TDB), whereas the TLR4 ligand LPS overcame inhibition by IL-4. Functionally, downregulation of Mincle expression by IL-4 was accompanied by reduced cytokine production upon stimulation with TDB. These inhibitory effects of IL-4 were dependent on the transcription factor Stat6. Together, our results show that the key Th2 cytokine IL-4 exerts a negative effect on the expression of Mincle and other Dectin-2 cluster CLR in mouse and human macrophages and DC, which may render these sentinel cells less vigilant for sensing mycobacterial and fungal ligands.nb_NO
dc.publisherFrontiers Medianb_NO
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleStat6-dependent inhibition of mincle expression in mouse and human antigen-presenting cells by the Th2 cytokine IL-4nb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.source.journalFrontiers in Immunologynb_NO
dc.relation.projectNorges forskningsråd: 223255nb_NO
dc.description.localcode© 2016 Hupfer, Schick, Jozefowski, Voehringer, Ostrop and Lang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).nb_NO
cristin.unitnameInstitutt for klinisk og molekylær medisin

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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal