IL-10/TGF-β–Modified Macrophages Induce Regulatory T Cells and Protect against Adriamycin Nephrosis

• Published in: Journal of the American Society of Nephrology Vol. 21; no. 6; pp. 933 - 942
• Main Authors: Cao, Qi, Wang, Yiping, Zheng, Dong, Sun, Yan, Wang, Ya, Lee, Vincent W.S., Zheng, Guoping, Tan, Thian Kui, Ince, Jon, Alexander, Stephen I., Harris, David C.H.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society of Nephrology 01.06.2010
• Subjects: Animals; B7-1 Antigen - metabolism; Basic Research; Biological and medical sciences; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - pathology; Cell Proliferation - drug effects; Cells, Cultured; Disease Models, Animal; Doxorubicin - adverse effects; Glomerulonephritis; Interleukin-10 - pharmacology; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Macrophages - drug effects; Macrophages - pathology; Male; Medical sciences; Mice; Mice, Inbred BALB C; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Nephrosis - chemically induced; Nephrosis - physiopathology; Nephrosis - prevention & control; Nitric Oxide Synthase Type II - metabolism; Phenotype; T-Lymphocytes, Regulatory - pathology; Transforming Growth Factor beta - pharmacology; V-Set Domain-Containing T-Cell Activation Inhibitor 1; Glomerulonephritis; Kidney disease; Antineoplastic agent; DNA topoisomerase (ATP-hydrolysing); Nephrology; Urinary system disease; Enzyme; Transforming growth factor β; Cytokine; Enzyme inhibitor; Nephrotic syndrome; Topoisomerase II inhibitor; Doxorubicin; Urology; Antibiotic; Isomerases; Interleukin 10; T-Lymphocyte; Anthracyclins; Regulatory cell; Macrophage
• DOI: 10.1681/ASN.2009060592
• ISSN: 1046-6673; 1533-3450

IL-10/TGF-beta-modified macrophages, a subset of activated macrophages, produce anti-inflammatory cytokines, suggesting that they may protect against inflammation-mediated injury. Here, macrophages modified ex vivo by IL-10/TGF-beta (IL-10/TGF-beta Mu2) significantly attenuated renal inflammation, structural injury, and functional decline in murine adriamycin nephrosis (AN). These cells deactivated effector macrophages and inhibited CD4+ T cell proliferation. IL-10/TGF-beta Mu2 expressed high levels of the regulatory co-stimulatory molecule B7-H4, induced regulatory T cells from CD4+CD25- T cells in vitro, and increased the number of regulatory T cells in lymph nodes draining the kidneys in AN. The phenotype of IL-10/TGF-beta Mu2 did not switch to that of effector macrophages in the inflamed kidney, and these cells did not promote fibrosis. Taken together, these data demonstrate that IL-10/TGF-beta-modified macrophages effectively protect against renal injury in AN and may become part of a therapeutic strategy for chronic inflammatory disease.