The renal microenvironment modifies dendritic cell phenotype

• Verfasst von: Chessa, Federica [VerfasserIn]
• Verfasst von: Mathow, Daniel Benjamin [VerfasserIn]
• Verfasst von: Wang, Shijun [VerfasserIn]
• Verfasst von: Hielscher, Thomas [VerfasserIn]
• Verfasst von: Porubský, Štefan [VerfasserIn]
• Verfasst von: Gretz, Norbert [VerfasserIn]
• Verfasst von: Gröne, Hermann-Josef [VerfasserIn]
• Verfasst von: Popovic, Zoran V. [VerfasserIn]
• Titel: The renal microenvironment modifies dendritic cell phenotype
• Verf.angabe: Federica Chessa, Daniel Mathow, Shijun Wang, Thomas Hielscher, Ann Atzberger, Stefan Porubsky, Norbert Gretz, Sven Burgdorf, Hermann-Josef Gröne and Zoran V. Popovic
• Jahr: 2016
• Umfang: 13 S.
• Fussnoten: Gesehen am 10.01.2019 ; Published online 14 October 2015
• Titel Quelle: Enthalten in: Kidney international
• Ort Quelle: New York, NY : Elsevier, 1972
• Jahr Quelle: 2016
• Band/Heft Quelle: 89(2016), 1, Seite 82-94
• ISSN Quelle: 1523-1755
• DOI: doi:10.1038/ki.2015.292
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: acute rejection
• Sach-SW: inflammation
• Sach-SW: renal pathology
• K10plus-PPN: 1586101846

Abstract

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.