Aboelnazar Salma, Ghoneim Hossam, Moaaz Mai, Bahgat Eman Taha, Shalaby Thanaa
Immunology Department, Medical Research Institute, University of Alexandria, Alexandria, Egypt.
Department of Immunology and Allergy, Medical Research Institute, University of Alexandria, Alexandria, Egypt.
Prz Gastroenterol. 2021;16(1):67-82. doi: 10.5114/pg.2021.104737. Epub 2021 Mar 26.
Type 1 diabetes mellitus is an autoimmune disorder characterized by inflammatory damage to pancreatic β cells resulting in loss of insulin secretion. In autoimmune type 1 diabetes mellitus (T1D) natural killer cells (NK) initiate pancreatic islets cell lyses in autoimmune T1D. Loss of T regulatory cells (Treg) at disease onset facilitates the 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.
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. suppressor assay was used to assess the suppressor effect of Treg cells after exogenous IL-2 treatment.
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 ( = 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) ( < 0.001), but the NK functions did not show any significant changes with prolonged treatment.
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.
1型糖尿病是一种自身免疫性疾病，其特征是胰腺β细胞受到炎症损伤，导致胰岛素分泌丧失。在自身免疫性1型糖尿病（T1D）中，自然杀伤细胞（NK）引发自身免疫性T1D中的胰岛细胞溶解。疾病发作时调节性T细胞（Treg）的丧失促进了NK细胞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Treg细胞，并加强对促炎性NK细胞的控制和调节。
需要研究这种关系，以改进旨在重置Treg细胞和促炎细胞之间平衡的治疗策略。
我们使用了负载在壳聚糖纳米颗粒上的低剂量IL-2的新型制剂。该研究包括116只经链脲佐菌素实验诱导的T1D BALB/c小鼠，分为几组。通过流式细胞术和酶联免疫吸附测定（ELISA）对它们的脾细胞进行短期培养，以评估CD4+FOXP3+ Treg细胞和NKp46+NK细胞的表达。进行了形态学、免疫组织化学和形态计量学分析。采用抑制试验评估外源性IL-2处理后Treg细胞的抑制作用。
与其他组相比，注射负载IL-2的壳聚糖纳米颗粒的小鼠中NK细胞表达、NKp46水平和NK细胞功能的调节更为明显。在负载0.3 μIU IL-2的壳聚糖中，Treg细胞和NK细胞表达之间存在统计学上的负相关（r = 0.047），这种相关性与Treg细胞上的FOXP3表达有关。在注射0.3 μIU持续较长时间（3周）的小鼠中，观察到NK和NKp46的表达发生改变（P < 0.001），但长期治疗后NK细胞功能未显示任何显著变化。
长期给予低剂量IL-2会导致NKp46的强烈表达，表明Treg细胞在NK细胞的刺激和激活中起重要作用。低剂量IL-2选择性调节NKp46+NK细胞和FOXP3+ Treg细胞，并增加它们的表达。
