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000120542 1001_ $$0P:(DE-He78)659b67be544344052284c48f7d49c7cd$$aPopovic, Zoran$$b0$$eFirst author$$udkfz
000120542 245__ $$aHyperosmolarity impedes the cross-priming competence of dendritic cells in a TRIF-dependent manner.
000120542 260__ $$aLondon$$bNature Publishing Group$$c2017
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000120542 520__ $$aTissue osmolarity varies among different organs and can be considerably increased under pathologic conditions. Hyperosmolarity has been associated with altered stimulatory properties of immune cells, especially macrophages and dendritic cells. We have recently reported that dendritic cells upon exposure to hypertonic stimuli shift their profile towards a macrophage-M2-like phenotype, resulting in attenuated local alloreactivity during acute kidney graft rejection. Here, we examined how hyperosmotic microenvironment affects the cross-priming capacity of dendritic cells. Using ovalbumin as model antigen, we showed that exposure of dendritic cells to hyperosmolarity strongly inhibits activation of antigen-specific T cells despite enhancement of antigen uptake, processing and presentation. We identified TRIF as key mediator of this phenomenon. Moreover, we detected a hyperosmolarity-triggered, TRIF-dependent clustering of MHCI loaded with the ovalbumin-derived epitope, but not of overall MHCI molecules, providing a possible explanation for a reduced T cell activation. Our findings identify dendritic cells as important players in hyperosmolarity-mediated immune imbalance and provide evidence for a novel pathway of inhibition of antigen specific CD8(+) T cell response in a hypertonic micromilieu.
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000120542 7001_ $$aEmbgenbroich, Maria$$b1
000120542 7001_ $$0P:(DE-HGF)0$$aChessa, Federica$$b2
000120542 7001_ $$0P:(DE-He78)9bce4efcbedb17d7b4d0d7832c136faf$$aNordström, Viola$$b3$$udkfz
000120542 7001_ $$0P:(DE-He78)dfbd048cb771a09543aad8eba5013468$$aBonrouhi, Mahnaz$$b4$$udkfz
000120542 7001_ $$00000-0003-1277-310X$$aHielscher, Thomas$$b5
000120542 7001_ $$aGretz, Norbert$$b6
000120542 7001_ $$0P:(DE-HGF)0$$aWang, Shijun$$b7
000120542 7001_ $$0P:(DE-HGF)0$$aMathow, Daniel$$b8
000120542 7001_ $$aQuast, Thomas$$b9
000120542 7001_ $$aSchloetel, Jan-Gero$$b10
000120542 7001_ $$aKolanus, Waldemar$$b11
000120542 7001_ $$aBurgdorf, Sven$$b12
000120542 7001_ $$0P:(DE-He78)00a2ea610aee4a8fca32908fc3d02e91$$aGröne, Hermann-Josef$$b13$$eLast author$$udkfz
000120542 773__ $$0PERI:(DE-600)2615211-3$$a10.1038/s41598-017-00434-y$$gVol. 7, no. 1, p. 311$$n1$$p311$$tScientific reports$$v7$$x2045-2322$$y2017
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