title: The renal microenvironment modifies dendritic cell phenotype.
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.
authors.affiliation: Department of Cellular and Molecular Pathology, Heidelberg, Germany.
authors.forename: Federica
authors.initials: F
authors.lastname: Chessa
authors.affiliation: Department of Cellular and Molecular Pathology, Heidelberg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mathow
authors.affiliation: Department of Cellular and Molecular Pathology, Heidelberg, Germany.
authors.forename: Shijun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Biostatistics, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hielscher
authors.affiliation: Flow Cytometry Core Facility, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Ann
authors.initials: A
authors.lastname: Atzberger
authors.affiliation: Department of Cellular and Molecular Pathology, Heidelberg, Germany; Institute of Pathology, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Porubsky
authors.affiliation: Medical Research Center, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Gretz
authors.affiliation: Department of Cellular Immunology, LIMES Institute, University of Bonn, Bonn, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Burgdorf
authors.affiliation: Department of Cellular and Molecular Pathology, Heidelberg, Germany. Electronic address: h.-j.groene@dkfz.de.
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gröne
authors.affiliation: Department of Cellular and Molecular Pathology, Heidelberg, Germany; Institute of Pathology, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany. Electronic address: z.popovic@dkfz.de.
authors.forename: Zoran V
authors.initials: ZV
authors.lastname: Popovic
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation; D020869:Gene Expression Profiling; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D006706:Homeostasis; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology; D016030:Kidney Transplantation; D007958:Leukocyte Count; D008264:Macrophages; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D009994:Osmolar Concentration; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology; D059467:Transcriptome
chemical_list: D011956:Receptors, Cell Surface; D012965:Sodium Chloride
keywords: acute rejection; inflammation; renal pathology