Remote ischemic conditioning causes CD4 T cells shift towards reduced cell-mediated inflammation
Remote ischemic conditioning causes CD4 T cells shift towards reduced cell-mediated inflammation
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DOI：
10.1007/s00383-022-05093-3
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发表时间：
2022-03-04
影响因子：
1.8
通讯作者：
Pierro, Agostino
中科院分区：
文献类型：
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作者：
Alganabi, Mashriq;Biouss, George;Pierro, Agostino
目的 坏死性小肠结肠炎 (NEC) 是一种新生儿胃肠道疾病，与免疫介导的肠道炎症有关。应用于肢体的远程缺血调节 (RIC) 已被证明可以预防实验性 NEC。在这项研究中，我们在该疾病的实验小鼠模型中探讨了 NEC 中涉及的免疫细胞介导的反应以及 RIC 的免疫调节作用。方法 在出生后第 5 天 (p5) 使用灌胃高渗配方、脂多糖和缺氧在 C57BL/6 小鼠（伦理批准#58119）幼崽中诱导 NEC。 RIC 包括 4 个周期，即在第 6 和第 8 代 NEC 诱导期间右后肢 5 分钟缺血，然后再灌注 5 分钟。母乳喂养的小鼠用作对照。在 p9 时处死小鼠，评估回肠组织的炎性细胞因子和 T 细胞群的特征。结果 NEC 小鼠的 CD4(+) 细胞数量增加，表明 T 细胞在 NEC 回肠间质中积累。与对照组相比，NEC 幼犬促炎细胞因子（GATA3、IFN γ、IL1 β、IL6、IL17、IL22 和 TNF α）表达上调，抗炎细胞因子（TGF β）表达减少。在 NEC 中，Treg/Th17 细胞的平衡也向 Th17 方向转变。与单独的 NEC 相比，NEC 过程中的 RIC 导致促炎细胞因子（GATA3、IFN γ、IL1 β、IL6、IL17、IL22 和 TNF α）减少，抗炎细胞因子 TGF β 增加，并伴随 Th17 细胞向 Treg 细胞转变。结论 在实验性 NEC 中，远程缺血调节减少了促炎标记物的产生并增加了抗炎标记物的产生。此外，在 NEC 过程中，RIC 逆转了 Treg/Th17 的不平衡，为其对细胞介导的炎症的作用提供了支持。 RIC 是一种非侵入性物理操作，对于减少 NEC 中出现的炎症具有显着的有益效果。
Purpose Necrotizing enterocolitis (NEC) is a gastrointestinal disease in neonates that is associated with immune-mediated intestinal inflammation. Remote ischemic conditioning (RIC) applied to a limb has been shown to be protective against experimental NEC. In this study, we explore the immune cell-mediated response involved in NEC and the immunomodulatory effects of RIC in an experimental mouse model of the disease. Methods NEC was induced in C57BL/6 mice (ethical approval #58119) pups on postnatal day5 (p5) using gavage hyperosmolar formula, lipopolysaccharide, and hypoxia. RIC consisted of 4 cycles of 5 min ischemia followed by 5 min reperfusion of the right hindlimb during NEC induction on p6 and p8. Breastfed mice were used as control. The mice were sacrificed on p9, with ileal tissue evaluated for inflammatory cytokines and by characterization of T-cell populations. Results NEC mice had increased number of CD4(+) cells indicating an accumulation of T-cells in the mesenchyme of the NEC ileum. Compared to control, NEC pups had upregulated expression pro-inflammatory cytokines (GATA3, IFN gamma, IL1 beta, IL6, IL17, IL22, and TNF alpha) and reduced anti-inflammatory cytokine (TGF beta). In NEC, there was also a shift in the balance of Treg/Th17 cells towards Th17. Compared to NEC alone, RIC during the course of NEC resulted in reduction of pro-inflammatory cytokines (GATA3, IFN gamma, IL1 beta, IL6, IL17, IL22, and TNF alpha), increase in anti-inflammatory cytokine TGF beta and concomitant shift back of Th17 cells towards Treg cells. Conclusion In experimental NEC, remote ischemic conditioning reduces the production of pro-inflammatory markers and increases the production of anti-inflammatory markers. In addition, during NEC, RIC reverses the imbalance of Treg/Th17 providing support for its effect on cell-mediated inflammation. RIC is a non-invasive physical maneuver that can have a significant beneficial effect in reducing the inflammation seen in NEC.