Introduction
Natural killer cells (NK) initiate pancreatic islets cell lyses in autoimmune type 1 diabetes mellitus (T1D). Loss of T regulatory cells (Treg) at disease onset facilitates activation and accumulation of NKs in the pancreatic microenvironment. A proper low dose interleukin 2 (IL-2) could enhance Tregs and enforce control and regulation of pro-inflammatory NKs. This relation needs to be studied to improve therapeutic strategies aimed at resetting the balance between Tregs and proinflammatory cells.

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). In vitro suppressor-assay was used in order 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 in mice injected with IL-2 loaded chitosan nanoparticles than 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 (three weeks) (p < 0.001) but the NK functions did not show any significant changes with prolonged treatment.

Conclusions
Low dose (0.3) µIU IL-2 nanoparticles effectively modulated NK and NKp46 expression. It selectively modulates the suppressive activity of Tregs indicating a significant role of Tregs in NK activation and function by controlling the availability of IL-2 in the microenvironment.



中文翻译：

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低剂量负载 IL-2 的壳聚糖纳米粒对实验诱导的自身免疫性 1 型糖尿病中自然杀伤细胞和调节性 T 细胞表达的影响

简介
自然杀伤细胞 (NK) 在自身免疫性 1 型糖尿病 (T1D) 中启动胰岛细胞裂解。疾病发作时 T 调节细胞 (Treg) 的缺失促进了 NK 在胰腺微环境中的激活和积累。适当的低剂量白细胞介素 2 (IL-2) 可以增强 Tregs 并加强对促炎 NKs 的控制和调节。需要研究这种关系以改善旨在重置 Treg 和促炎细胞之间平衡的治疗策略。

材料与方法
我们使用负载在壳聚糖纳米颗粒上的低剂量 IL-2 的新配方。该研究包括由链脲佐菌素实验诱导的 116 只 T1D BALB/c 小鼠，分为几组。将他们的脾细胞维持在短期培养物中，通过流式细胞术和酶联免疫测定法 (ELISA) 评估 CD4+Foxp3+ Treg 和 NKp46+NK 的表达。为了评估外源性 IL-2 处理后 Treg 细胞的抑制作用，使用了体外抑制试验。

结果
与其他组相比，在注射了负载 IL-2 的壳聚糖纳米粒子的小鼠中，NK 细胞表达、NKp46 水平和 NK 细胞功能受到调节。在负载 IL-2 的壳聚糖（0.3 µIU）中发现 Treg 和 NK 细胞表达之间存在统计负相关（p = 0.047），这种相关性与 Treg 细胞上的 Foxp3 表达有关。NK 和 NKp46 的修饰表达在注射 (0.3 µIU) 的小鼠中观察到更长的持续时间（三周）（p < 0.001），但 NK 功能在长期治疗中没有显示出任何显着变化。

结论
低剂量 (0.3) µIU IL-2 纳米颗粒有效调节 NK 和 NKp46 表达。它通过控制微环境中 IL-2 的可用性选择性地调节 Tregs 的抑制活性，表明 Tregs 在 NK 激活和功能中的重要作用。