Adoptive transfer of bone marrow dendritic cells failed to localize in the renal cortex and to improve renal injury in adriamycin nephropathy

Nephron Exp Nephrol. 2014;126(1):8-15. doi: 10.1159/000358086. Epub 2014 Feb 11.

Abstract

Background and aims: Murine bone marrow (BM) dendritic cells (DCs) can be modulated to be tolerogenic by cytokines, such as interleukin (IL)-10 and transforming growth factor (TGF)-β, and may play a regulatory role and sustain immune hemostasis in cognate kidney disease. However, it is unknown whether BM-DCs can be used to protect against renal injury in murine Adriamycin nephropathy (AN).

Methods: In this study, by adoptive in vivo transfer of BM-DCs, including immature DCs, mature DCs (lipopolysaccharide-stimulated DCs) and BM regulatory DCs (IL-10/TGF-β-modified DCs, DCregs), we addressed the potential benefits of BM-DCs in chronic kidney disease.

Results: We found that after adoptive transfer of DCregs, renal injury, including glomerulosclerosis, interstitial fibrosis and tubular atrophy, was not changed compared to AN controls. Correspondingly, renal functions measured by serum creatinine, 12-hour urine protein and creatinine clearance were also not improved by transfusion with DCregs compared to AN controls.

Conclusion: This study showed that the adoptive transfer of BM-DCs was unable to improve renal injury in an AN model, and this failure related to their inability to access the kidney.

MeSH terms

  • Adoptive Transfer
  • Animals
  • B7-1 Antigen / immunology
  • B7-1 Antigen / metabolism
  • B7-2 Antigen / immunology
  • B7-2 Antigen / metabolism
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Cells, Cultured
  • Chemokines / genetics
  • Chemokines / immunology
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / transplantation
  • Doxorubicin
  • Flow Cytometry
  • Gene Expression / immunology
  • Kidney Cortex / immunology*
  • Kidney Cortex / metabolism
  • Kidney Diseases / chemically induced
  • Kidney Diseases / immunology*
  • Kidney Diseases / therapy
  • Lipopolysaccharides / immunology
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / immunology
  • Renal Insufficiency, Chronic / immunology*
  • Renal Insufficiency, Chronic / therapy
  • Reverse Transcriptase Polymerase Chain Reaction
  • Treatment Failure

Substances

  • B7-1 Antigen
  • B7-2 Antigen
  • Chemokines
  • Cytokines
  • Lipopolysaccharides
  • Receptors, Chemokine
  • Doxorubicin