Potential therapeutic effects of interleukin-35 on the differentiation of naïve T cells into Helios(+)Foxp3(+) Tregs in clinical and experimental acute respiratory distress syndrome.
Potential therapeutic effects of interleukin-35 on the differentiation of naïve T cells into Helios(+)Foxp3(+) Tregs in clinical and experimental acute respiratory distress syndrome.
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IL-35 对临床和实验急性呼吸窘迫综合征中幼稚 T 细胞分化为 Helios Foxp3 Tregs 的潜在治疗作用
DOI：
10.1016/j.molimm.2021.01.009
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发表时间：
2021-04
影响因子：
3.6
通讯作者：
Xu F
中科院分区：
文献类型：
--
作者：
Wang C;Xie K;Li K;Lin S;Xu F
调节性T淋巴细胞是治疗急性呼吸窘迫综合征（ARDS）的重要靶点。IL-35是一种新发现的IL-12细胞因子家族成员，通过调节Treg细胞分化在多种免疫系统疾病中发挥重要的保护作用;然而，IL-35在ARDS发病机制中的作用仍不清楚。在这里，我们发现，与对照组相比，成人ARDS患者的IL-35显著升高。此外，IL-35与IL-6、IL-10及氧合指数（PaO 2/FiO 2）呈正相关，与TNF-α、IL-1β及APACHE II评分呈负相关。ARDS患者外周血Treg/CD 4+细胞比例及PMBCs中NF-κB的表达均显著高于健康对照组。重组IL-35改善CLP诱导的ARDS小鼠模型的存活率。此外，IL-35给药降低了炎症反应，如CLP诱导的ARDS中较低水平的细胞因子（包括IL-2、TNF-α、IL-1β和IL-6）和较少的肺损伤所反映的。重组IL-35可降低CLP诱导的ARDS模型肺组织细胞凋亡和NF-κB信号的表达，增加脾脏和外周血Treg细胞的比例。体外实验表明，IL-35可以影响初始CD 4 + T淋巴细胞分化为Foxp 3 +Helios+ TcB过程中STAT 5的磷酸化。我们的研究结果表明，IL-35通过促进幼稚CD 4 + T细胞分化为Foxp 3 +Helios+ Tcells来减轻ARDS，从而为抗ARDS治疗提供了一种新的工具。
Regulatory T lymphocytes are important targets for the treatment of acute respiratory distress syndrome (ARDS). IL-35 is a newly identified IL-12 cytokine family member that plays an important protective role in a variety of immune system diseases by regulating Treg cell differentiation; however, the role of IL-35 in the pathogenesis of ARDS is still unclear. Here, we found that IL-35 was significantly elevated in adult patients with ARDS compared to controls. Additionally, IL-35 was positively and significantly correlated with IL-6, IL-10 and the oxygenation index (PaO2/FiO2 ratio) but negatively correlated with TNF-α, IL-1β and APACHE II score during ARDS. Moreover, the proportion of Treg/CD4+ cells in the peripheral blood of ARDS patients and the expression of NF-κB in PMBCs were significantly higher than in healthy individuals. Recombinant IL-35 improved survival in a murine model of CLP-induced ARDS. Additionally, IL-35 administration decreased the inflammatory response, as reflected by lower levels of cytokines (including IL-2, TNF-α, IL-1β and IL-6) and less lung damage in CLP-induced ARDS. Furthermore, recombinant IL-35 reduced the apoptosis of lung tissue and the expression of NF-κB signalling in a CLP-induced ARDS model and increased the proportion of Treg cells in spleen and peripheral blood. In vitro experiments revealed that IL-35 can affect the phosphorylation of STAT5 during differentiation of naïve CD4+ T lymphocytes into Foxp3+Helios+ Tregs. Our findings suggest that IL-35 attenuates ARDS by promoting the differentiation of naïve CD4+ T cells into Foxp3+Helios+ Tregs, thereby providing a novel tool for anti-ARDS therapy.
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影响因子：
5.6
作者：
Jha P;Das H
通讯作者：
Das H
影响因子：
2.7
作者：
Wang C;Chen Q;Cui Z;Xu Z;Shi Y;Su S;Qi L;Geng Y;Liu R
通讯作者：
Liu R
影响因子：
3.7
作者：
Akimova T;Beier UH;Wang L;Levine MH;Hancock WW
通讯作者：
Hancock WW
DOI：
10.3760/cma.j.issn.1009-2587.2018.07.010
发表时间：
2018-07-20
影响因子：
--
作者：
Cui, P;Xin, H M;Tong, Y L
通讯作者：
Tong, Y L
影响因子：
3.8
作者：
Hsu, Jun-Te;Kan, Wen-Hong;Chaudry, Irshad H.
通讯作者：
Chaudry, Irshad H.