Low-dose interleukin-2-loaded nanoparticle effect on NK and T-reg cell expression in experimentally induced type 1 diabetes mellitus

低剂量白细胞介素-2 纳米粒子对实验性 1 型糖尿病中 NK 和 T-reg 细胞表达的影响

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作者:Salma Aboelnazar, Hossam Ghoneim, Mai Moaaz, Eman Taha Bahgat, Thanaa Shalaby

Aim

This relation needs to be studied to improve therapeutic strategies aimed at resetting the balance between Tregs and proinflammatory cells. Material and

Conclusions

Prolonged administration of low-dose IL-2 results in the vigorous expression of NKp46, indicating a significant role of Tregs in NK stimulation and motivation. Low-dose IL-2 selectively modulates NKp46 NK and FOXP3+ Tregs and increases their expression.

Material and methods

We used novel formulations of low-dose IL-2 loaded on chitosan nanoparticles. The study included 116 T1D BALB/c mice experimentally induced by streptozotocin, divided into groups. Their splenocytes were maintained in a short-term culture for assessment of expression of CD4+FOXP3+ Treg and NKp46+NK by both flow cytometry and enzyme-linked immunoassay (ELISA). Morphological, immunohistochemical, and morphometrical analyses were done. In vitro suppressor assay was used to assess the suppressor effect of Treg cells after exogenous IL-2 treatment.

Methods

We used novel formulations of low-dose IL-2 loaded on chitosan nanoparticles. The study included 116 T1D BALB/c mice experimentally induced by streptozotocin, divided into groups. Their splenocytes were maintained in a short-term culture for assessment of expression of CD4+FOXP3+ Treg and NKp46+NK by both flow cytometry and enzyme-linked immunoassay (ELISA). Morphological, immunohistochemical, and morphometrical analyses were done. In vitro suppressor assay was used to assess the suppressor effect of Treg cells after exogenous IL-2 treatment.

Results

NK cell expression, NKp46 level, and NK cell functions were modulated more in mice injected with IL-2-loaded chitosan nanoparticles than in other groups. A statistical inverse correlation was found between Treg and NK cell expression in IL-2-loaded chitosan with 0.3 µIU (p = 0.047), and this correlation was related to FOXP3 expression on Treg cells. The modified expression of NK and NKp46 was noticed in mice injected with 0.3 µIU for longer duration (3 weeks) (p < 0.001), but the NK functions did not show any significant changes with prolonged treatment. Conclusions: Prolonged administration of low-dose IL-2 results in the vigorous expression of NKp46, indicating a significant role of Tregs in NK stimulation and motivation. Low-dose IL-2 selectively modulates NKp46 NK and FOXP3+ Tregs and increases their expression.

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