| First Author | Bertelli R | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 10 | Pages | e111285 |
| PubMed ID | 25343479 | Mgi Jnum | J:223543 |
| Mgi Id | MGI:5649482 | Doi | 10.1371/journal.pone.0111285 |
| Citation | Bertelli R, et al. (2014) LPS nephropathy in mice is ameliorated by IL-2 independently of regulatory T cells activity. PLoS One 9(10):e111285 |
| abstractText | 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. |
