Modulatory effect of interleukin-2 loaded chitosan nano sphere on regulatory T cell activity in streptozotocin-induced diabetic mice

Objective: The current study aimed to assess the modulating effect of IL-2 encapsulated chitosan-nanoparticles (CSNPs) on the function of Treg cells through induction of type 1 diabetes (T1D). Treg cell function was monitored by the forkhead box P3 (FoxP3) and transforming growth factor beta (TGFβ) levels, correlating them with blood glucose and serum insulin levels.

Materials and methods: In this case-control study, a low dose of IL-2 (free and chitosan-loaded) was injected into a diabetic mice group. The levels of FoxP3 and TGF-β 1 were assessed using Enzyme-Linked Immunosorbent Assay. In addition, blood glucose and serum insulin levels were determined.

Results: The mean glucose level decreased significantly after free rIL-2 or rIL-2 / CSNPs treatment. Meanwhile, the mean serum insulin level was significantly increased after treatment with free rIL-2 or rIL-2/CSNPs. The mean levels of FoxP3 and TGFβ 1 were significantly increased with either free rIL-2 or rIL-2/CSNPs compared to the T1D untreated group (P < 0.001). In the treated mice group receiving free CSNPs, there was a significant negative correlation between glucose and insulin levels. Moreover, FoxP3 & TGFβ 1 levels had a significant positive correlation. In treated mice groups with free rIL-2 and IL-2 CSNPs, there was a significant positive correlation between FoxP3 and glucose levels. A significant negative correlation was found after conducting a correlation between insulin level and FoxP3 in the T1D/ rIL-2 / CSNPs group.

Conclusions: Low-dose IL-2 selectively modulates FoxP3 + Tregs, and TGFβ 1 increases their levels. These results demonstrated that IL-2-free and chitosan-loaded nanoparticles can be therapeutic agents in T1D.