LPS Nephropathy in Mice Is Ameliorated by IL-2 Independently of Regulatory T Cells Activity

• Published in: PloS one Vol. 9; no. 10; p. e111285
• Main Authors: Bertelli, Roberta, Di Donato, Armando, Cioni, Michela, Grassi, Fabio, Ikehata, Masami, Bonanni, Alice, Rastaldi, Maria Pia, Ghiggeri, Gian Marco
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.10.2014; Public Library of Science (PLoS)
• Subjects: Adenosine Triphosphate - metabolism; Analysis; Animal models; Animals; B cells; Biology and Life Sciences; CD4 antigen; Extracellular Space - metabolism; Hemodialysis; Histology; Hospitals; Humans; Immunoregulation; Immunosuppressive agents; Interleukin 2; Interleukin-2 - pharmacology; Interleukin-2 - therapeutic use; Kidney diseases; Kidney Diseases - chemically induced; Kidney Diseases - drug therapy; Kidney Diseases - immunology; Kidney Diseases - pathology; Kidneys; Laboratories; Lesions; Lipopolysaccharides; Lymph nodes; Lymphocytes; Lymphocytes T; Male; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mutation; Nephrology; Nephropathy; Nephrotic syndrome; Pathogenesis; Proteinuria; Proteinuria - complications; Proteinuria - urine; Rodents; Spleen; T cells; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; Toll-Like Receptor 4 - metabolism; Transplants & implants; Trends; United States > US; Italy; Switzerland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0111285

Immunosuppressive regulatory T cells (Tregs) have been hypothesized to exert a protective role in animal models of spontaneous (Buffalo/Mna) and/or drug induced (Adriamycin) nephrotic syndrome. In this study, we thought to define whether Tregs can modify the outcome of LPS nephropathy utilizing IL-2 as inducer of tissue and circulating Tregs. LPS (12 mg/Kg) was given as single shot in C57BL/6, p2rx7⁻/⁻ and Foxp3EGFP; free IL-2 (18.000 U) or, in alternative, IL-2 coupled with JES6-1 mAb (IL-2/anti-IL-2) were injected before LPS. Peripheral and tissue Tregs/total CD4+ cell ratio, urinary parameters and renal histology were evaluated for 15 days. IL-2 administration to wild type mice had no effect on peripheral Tregs number, whereas a significant increase was induced by the IL-2/anti-IL-2 immunocomplex after 5 days. Spleen and lymph nodes Tregs were comparably increased. In p2rx7⁻/⁻ mice, IL-2/anti-IL-2 treatment resulted in increase of peripheral Tregs but did not modify the spleen and lymph nodes quota. LPS induced comparable and transient proteinuria in both wild type and p2rx7⁻/⁻ mice. Proteinuria was inhibited by co-infusion of human IL-2, with reduction at each phase of the disease (24 -48 and 72 hours) whereas IL-2/anti-IL-2 produced weaker effects. In all mice (wild type and p2rx7⁻/⁻) and irrespective of treatment (IL-2, IL-2/anti-IL-2), LPS was associated with progressive signs of renal pathologic involvement resulting in glomerulosclerosis. In conclusion, IL-2 plays a transient protective effect on proteinuria induced by LPS independent of circulating or tissue Tregs but does not modify the outcome of renal degenerative renal lesions.