TY  - JOUR
AU  - Popovic, Zoran
AU  - Embgenbroich, Maria
AU  - Chessa, Federica
AU  - Nordström, Viola
AU  - Bonrouhi, Mahnaz
AU  - Hielscher, Thomas
AU  - Gretz, Norbert
AU  - Wang, Shijun
AU  - Mathow, Daniel
AU  - Quast, Thomas
AU  - Schloetel, Jan-Gero
AU  - Kolanus, Waldemar
AU  - Burgdorf, Sven
AU  - Gröne, Hermann-Josef
TI  - Hyperosmolarity impedes the cross-priming competence of dendritic cells in a TRIF-dependent manner.
JO  - Scientific reports
VL  - 7
IS  - 1
SN  - 2045-2322
CY  - London
PB  - Nature Publishing Group
M1  - DKFZ-2017-00971
SP  - 311
PY  - 2017
AB  - Tissue 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:28331179
C2  - pmc:PMC5428499
DO  - DOI:10.1038/s41598-017-00434-y
UR  - https://inrepo02.dkfz.de/record/120542
ER  -