TY  - JOUR
AU  - Chessa, Federica
AU  - Mathow, Daniel
AU  - Wang, Shijun
AU  - Hielscher, Thomas
AU  - Atzberger, Ann
AU  - Porubsky, Stefan
AU  - Gretz, Norbert
AU  - Burgdorf, Sven
AU  - Gröne, Hermann-Josef
AU  - Popovic, Zoran
TI  - The renal microenvironment modifies dendritic cell phenotype.
JO  - Kidney international
VL  - 89
IS  - 1
SN  - 0085-2538
CY  - Basingstoke
PB  - Nature Publishing Group
M1  - DKFZ-2017-01762
SP  - 82 - 94
PY  - 2016
AB  - Renal dendritic cells are a major component of the renal mononuclear phagocytic system. In the renal interstitium, these cells are exposed to an osmotic gradient, mainly sodium, whose concentration progressively increases towards inner medulla. Renal allograft rejection affects predominantly the cortex, suggesting a protective role of the renal medullary micromilieu. Whether osmolar variations can modulate the function of renal dendritic cells is currently undefined. Considering the central role of dendritic cells in promoting allorejection, we tested whether the biophysical micromilieu, particularly the interstitial osmotic gradient, influences their alloreactivity. There was a progressive depletion of leukocytes towards the medulla of homeostatic kidney. Only macrophages opposed this tendency. Flow cytometry of homeostatic and post-transplant medullary dendritic cells revealed a switch towards a macrophage-like phenotype. Similarly, bone marrow-derived dendritic cells developed ex vivo in sodium chloride-enriched medium acquired a M2-like signature. Microarray analysis of allotransplant dendritic cells posed a medullary downregulation of genes mainly involved in alloantigen recognition. Gene expression profiles of both medullary dendritic cells and bone marrow-derived dendritic cells matured in hyperosmolar medium had an overlap with the macrophage M2 signature. Thus, the medullary environment inhibits an alloimmune response by modulating the phenotype and function of dendritic cells.
KW  - Receptors, Cell Surface (NLM Chemicals)
KW  - Sodium Chloride (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26466317
DO  - DOI:10.1038/ki.2015.292
UR  - https://inrepo02.dkfz.de/record/125636
ER  -