CD4+CD126low/- Foxp3+ Cell Population Represents a Superior Subset of Regulatory T Cells in Treating Autoimmune Diseases
CD4+CD126low/- Foxp3+ Cell Population Represents a Superior Subset of Regulatory T Cells in Treating Autoimmune Diseases
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CD4( )CD126(低/-) Foxp3( ) 细胞群是治疗自身免疫性疾病的调节性 T 细胞的优质亚群
DOI：
10.1016/j.ymthe.2020.07.020
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发表时间：
2020-11-04
影响因子：
12.4
通讯作者：
Zheng, Song Guo
中科院分区：
文献类型：
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作者：
Chen, Ye;Xu, Zhenjian;Zheng, Song Guo
CD4(+)Foxp3（+）调节性T （Treg）细胞对于维持体内平衡和预防自身免疫性疾病至关重要。尽管如此，我们和其他人之前报道过天然Treg细胞在高盐饮食的炎症环境中不稳定和功能失调，限制了Treg在疾病控制中的功能。在这项研究中，我们做了一个创新的观察，显示Treg池内的高度异质性。我们发现CD126，白细胞介素(IL)-6受体α链，有助于Treg细胞的不稳定性。通过一系列体外和体内实验方法，我们证明了CD126(Lo/-) Treg细胞比CD126(Hi) nTreg细胞具有更大的功能和更稳定，即使在IL-6和炎症存在的情况下也是如此。程序性死亡-1 （PD-1）阻断阻断CD126(Lo/-) nTreg细胞的稳定性。此外，CD126(Lo/-) Treg细胞可以治疗结肠炎和已建立的胶原诱导的关节炎，而CD126（Hi）细胞群不能做到这一点。此外，我们注意到Treg细胞的CD126表达与类风湿关节炎（RA）的严重程度和Treg细胞的稳定性呈正相关。我们的研究结果强烈表明，CD126(Lo/-) nTreg细胞的操纵可能是治疗自身免疫性疾病和与Treg细胞缺陷相关的其他疾病的一种新策略。
CD4(+)Foxp3(+) regulatory T (Treg) cells are crucial for maintaining homeostasis and preventing autoimmune diseases. Nonetheless, we and others have previously reported that natural Treg cells are unstable and dysfunctional in the inflamed environment with a high-salt diet, limiting the Treg function in disease control. In this study, we made an innovative observation showing a high degree of heterogeneity within the Treg pool. We identified that CD126, interleukin (IL)-6 receptor alpha chain, contributed to Treg cell instability. Using a series of in vitro and in vivo experimental approaches, we demonstrated that CD126(Lo/-) Treg cells presented greater function and were more stable than CD126(Hi) nTreg cells, even in the presence of IL-6 and inflammation. Blockade of programmed death-1 (PD-1) interrupted CD126(Lo/-) nTreg cell stability. Additionally, CD126(Lo/-) Treg cells can treat colitis and established collagen-induced arthritis, while the CD126(Hi) cell population failed to do this. Moreover, we noted that CD126 expression of Treg cells had a positive correlation to rheumatoid arthritis (RA) severity and the stability of Treg cells. Our results strongly suggest that the manipulation of CD126(Lo/-) nTreg cells could be a novel strategy for the treatment of autoimmune diseases and for other conditions associated with a deficit of Treg cells.