Facoltà di scienze biomediche

LPS nephropathy in mice is ameliorated by IL-2 independently of regulatory T cells activity

Bertelli, Roberta ; Di Donato, Armando ; Cioni, Michela ; Grassi, Fabio ; Ikehata, Masami ; Bonanni, Alice ; Rastaldi, Maria Pia ; Ghiggeri, Gian Marco

In: Plos one, 2014, vol. 9, no. 10, p. e111285

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,... More

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    Summary
    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.