IL-2/IL-2Ab Complexes Induce Regulatory T Cell Expansion and Protect against Proteinuric CKD

Abstract

Regulatory T cells (Tregs) help protect against autoimmune renal injury. The use of agonist antibodies and antibody/cytokine combinations to expand Tregs in vivo may have therapeutic potential for renal disease. Here, we investigated the effects of administering IL-2/IL-2Ab complexes in mice with adriamycin nephropathy, a model of proteinuric kidney disease that resembles human focal segmental glomerulosclerosis. Injecting IL-2/IL-2Ab complexes before or, to a lesser extent, after induction of disease promoted expansion of Tregs. Furthermore, administration of this complex was renoprotective, evidenced by improved renal function, maintenance of body weight, less histologic injury, and reduced inflammation. IL-2/IL-2Ab reduced serum IL-6 and renal expression of IL-6 and IL-17 but enhanced expression of IL-10 and Foxp3 in the spleen. In vitro, the addition of IL-2/IL-2Ab complexes induced rapid STAT-5 phosphorylation in CD4 T cells. In summary, these data suggest that inducing the expansion of Tregs by administering IL-2/IL-2Ab complexes is a possible strategy to treat renal disease.

Nitro-oleic acid protects against adriamycin-induced nephropathy in mice

“…Inflammation is an important component of the pathophysiology of ADR nephropathy (7,22,26,33). Histological assessment of the kidneys of ADR-treated mice shows tubulointerstitial inflammation with infiltration of T and B lymphocytes and macrophages.…”

Interleukin-2: Biology, Design and Application

“…These data would rather argue against IL-2R crosslinking by IL-2/ S4B6 complexes. For IL-2/JES6-1 complexes, STAT5 phosphorylation was reduced in CD25 + YT-1 human NK cells compared with IL-2 in vitro [13], although another report using in vitro stimulation of total mouse splenocytes suggested that, compared with IL-2, IL-2/JES6-1 complexes led to increased STAT5 phosphorylation in CD4 + T cells [71]. In line with the former Recent structural data not only provide evidence for the steric aspects of the abovementioned model but also suggest mild antagonistic and allosteric forces at work (Figure 3).…”

IL-2/Anti-IL-2 Complex Attenuates Renal Ischemia-Reperfusion Injury through Expansion of Regulatory T Cells

“…Furthermore, the IL-2C treatment showed its therapeutic potential in adriamycin nephropathy, a form of CKD. 11 However, there has been no study for the effect of the IL-2C on AKI. Here, we investigated whether the IL-2C can attenuate renal IRI by inducing Tregs using murine models.…”