Adiponectin/AdipoR1 Axis Promotes IL-10 Release by Human Regulatory T Cells.
Adiponectin/AdipoR1 Axis Promotes IL-10 Release by Human Regulatory T Cells.
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DOI：
10.3389/fimmu.2021.677550
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发表时间：
2021
影响因子：
7.3
通讯作者：
Bossios A
中科院分区：
文献类型：
--
作者：
Ramos-Ramírez P;Malmhäll C;Tliba O;Rådinger M;Bossios A
脂联素是炎症状态下一种重要的免疫调节介质。此前我们已表明脂联素受体1（AdipoR1）在小鼠调节性T细胞（Tregs）中表达，但其在人调节性T细胞中的表达情况仍不清楚。在此，我们检测了AdipoR1在人调节性T细胞中的表达，以及其配体球状脂联素（gAd）是否会影响调节性T细胞分泌白细胞介素-10（IL - 10）的能力，还有2型（T2）炎症在此过程中所起的作用。
通过流式细胞术分析人外周血调节性T细胞中AdipoR1、Helios和IL - 10的表达。从外周血单个核细胞（PBMCs）中富集的CD4 + T细胞，分别在有或无gAd、化学合成的脂联素受体激动剂AdipoRon的条件下，或在T2细胞因子环境中培养。随后利用流式细胞术评估细胞内IL - 10、分泌IL - 10的细胞、叉头框蛋白P3（FOXP3）和Helios的表达，以及磷酸化的p38丝裂原活化蛋白激酶（MAPK）。采用酶联免疫吸附试验（ELISA）对CD4 + T细胞培养上清中的IL - 10水平进行定量检测。
我们发现人调节性T细胞中有一部分表达AdipoR1。重要的是，Helios阴性细胞中AdipoR1的表达高于Helios阳性细胞。同样，与Helios阳性AdipoR1阳性调节性T细胞相比，Helios阴性AdipoR1阳性调节性T细胞中IL - 10阳性细胞的频率更高。相反，Helios阳性AdipoR1阳性调节性T细胞中IL - 10的平均荧光强度（MFI）高于Helios阴性AdipoR1阳性调节性T细胞。当用人CD4 + T细胞分别与gAd或AdipoRon孵育时，Helios阴性AdipoR1阳性调节性T细胞中IL - 10的分泌、FOXP3的表达以及p38 MAPK的磷酸化均显著增加。有趣的是，在T2细胞因子环境下，gAd显著增加了细胞内IL - 10水平，主要是在Helios阳性AdipoR1阳性调节性T细胞中，同时CD4 + T细胞培养上清中的IL - 10水平也有所增加。
综上所述，我们的研究结果表明，脂联素/AdipoR1轴可促进调节性T细胞释放IL - 10，主要是在Helios阴性调节性T细胞中，并且T2炎症可增强Helios阳性调节性T细胞中的这种效应。
Adiponectin is an important immunomodulatory mediator in inflammatory conditions. While we previously showed that adiponectin receptor 1 (AdipoR1) is expressed in murine regulatory T cells (Tregs), its expression in human Tregs remain unknown. Here, we examined the expression of AdipoR1 in human Tregs and whether its ligand, globular adiponectin (gAd) affects the Treg ability to secrete IL-10 and the role of Type 2 (T2) inflammation in such process. Human Tregs from peripheral blood were analyzed by flow cytometry for AdipoR1, Helios and IL-10 expression. CD4+ T cells enriched from peripheral blood mononuclear cells (PBMCs) were cultured in the presence or the absence of gAd or the chemical adiponectin receptor agonist, AdipoRon, or in a T2 cytokine milieu. Flow cytometry was then used to assess intracellular IL-10, IL-10 secreting cells, FOXP3 and Helios expression, and phosphorylated p38 MAP kinase (MAPK). IL-10 levels in CD4+ T cell supernatants were quantified by ELISA. We found that a subset of human Tregs expressed AdipoR1. Importantly, more Helios- cells expressed AdipoR1 than Helios+ cells. Likewise, there was a higher frequency of IL-10+ cells within Helios- AdipoR1+ Tregs compared to Helios+ AdipoR1+ Tregs. In contrast, the IL-10 mean fluorescence intensity (MFI) was higher in Helios+ AdipoR1+ Tregs compared to Helios-AdipoR1+ Tregs. When human CD4+ T cells were treated with gAd or AdipoRon, a significant increase in IL-10 secretion, FOXP3 expression, and p38 MAPK phosphorylation was observed in Helios- AdipoR1+ Tregs. Interestingly, gAd under T2 cytokine milieu significantly increased the intracellular levels of IL-10, mainly in Helios+ AdipoR1+ Tregs, and IL-10 levels in supernatants of CD4+ T cells. Collectively, our findings suggest that adiponectin/AdipoR1 axis promotes IL-10 release by Tregs, mainly in Helios- Tregs, and the effect was amplified by T2 inflammation in Helios+ Tregs.
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影响因子：
3.7
作者：
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通讯作者：
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3.6
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通讯作者：
Drake CG