Lipopolysaccharide-pretreated plasmacytoid dendritic cells ameliorate experimental chronic kidney disease.
Plasmacytoid dendritic cells play important roles in inducing immune tolerance, preventing allograft rejection, and regulating immune responses in both autoimmune disease and graft-versus-host disease. In order to evaluate a possible protective effect of plasmacytoid dendritic cells against renal inflammation and injury, we purified these cells from mouse spleens and adoptively transferred lipopolysaccharide (LPS)-treated cells, modified ex vivo, into mice with adriamycin nephropathy. These LPS-treated cells localized to the kidney cortex and the lymph nodes draining the kidney, and protected the kidney from injury during adriamycin nephropathy. Glomerulosclerosis, tubular atrophy, interstitial expansion, proteinuria, and creatinine clearance were significantly reduced in mice with adriamycin nephropathy subsequently treated with LPS-activated plasmacytoid dendritic cells as compared to the kidney injury in mice given naive plasmacytoid dendritic cells. In addition, LPS-pretreated cells, but not naive plasmacytoid dendritic cells, convert CD4+CD25- T cells into Foxp3+ regulatory T cells and suppress the proinflammatory cytokine production of endogenous renal macrophages. This may explain their ability to protect against renal injury in adriamycin nephropathy.
Centre for Transplant and Renal Research, Westmead Millennium Institute, The University of Sydney, Sydney, New South Wales, Australia.
Dong
D
Zheng
Qi
Q
Cao
Vincent W S
VW
Lee
Ya
Y
Wang
Guoping
G
Zheng
YuanMin
Y
Wang
Thian Kui
TK
Tan
Changqi
C
Wang
Stephen I
SI
Alexander
David C H
DC
Harris
Yiping
Y
Wang
D019264:Adoptive Transfer; D000818:Animals; D001284:Atrophy; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D002908:Chronic Disease; D018920:Coculture Techniques; D003404:Creatinine / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation*; D004195:Disease Models, Animal; D004317:Doxorubicin; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005921:Glomerulonephritis / Q000276:immunology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007668:Kidney / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008198:Lymph Nodes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009395:Nephritis, Interstitial / Q000276:immunology / Q000517:prevention & control; D010641:Phenotype; D011507:Proteinuria / Q000276:immunology / Q000517:prevention & control; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D015415:Biomarkers; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C508018:Il2ra protein, mouse; D018836:Inflammation Mediators; D053645:Interleukin-2 Receptor alpha Subunit; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D004317:Doxorubicin; D003404:Creatinine