title: LPS nephropathy in mice is ameliorated by IL-2 independently of regulatory T cells activity.
abstract: 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.
authors.affiliation: Division of Nephrology, Dialysis, Transplantation and Laboratory on Physiopathology of Uremia, Giannina Gaslini Children Hospital, Genoa, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Bertelli
authors.affiliation: Division of Nephrology, Dialysis, Transplantation and Laboratory on Physiopathology of Uremia, Giannina Gaslini Children Hospital, Genoa, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Di Donato
authors.affiliation: Division of Nephrology, Dialysis, Transplantation and Laboratory on Physiopathology of Uremia, Giannina Gaslini Children Hospital, Genoa, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Cioni
authors.affiliation: Institute for Research in Biomedicine, Bellinzona, Switzerland; Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Grassi
authors.affiliation: Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy.
authors.forename: Masami
authors.initials: M
authors.lastname: Ikehata
authors.affiliation: Division of Nephrology, Dialysis, Transplantation and Laboratory on Physiopathology of Uremia, Giannina Gaslini Children Hospital, Genoa, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Bonanni
authors.affiliation: Renal Research Laboratory, Fondazione Istituto di Ricerca e Cura a carattere Scientifico (IRCCS ) Ca' Granda Ospedale Maggiore Policlinico and Fondazione D'Amico per la Ricerca sulle Malattie Renali, Milano, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Rastaldi
authors.affiliation: Division of Nephrology, Dialysis, Transplantation and Laboratory on Physiopathology of Uremia, Giannina Gaslini Children Hospital, Genoa, Italy.
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D008070:Lipopolysaccharides; D008297:Male; D008810:Mice, Inbred C57BL; D011507:Proteinuria / Q000150:complications / Q000652:urine; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D007376:Interleukin-2; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D000255:Adenosine Triphosphate