HO-1 regulates the function of Treg: Association with the immune intolerance in vitiligo.
HO-1 regulates the function of Treg: Association with the immune intolerance in vitiligo.
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HO-1调节Treg功能：与白癜风免疫不耐受的关系
DOI：
10.1111/jcmm.13723
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发表时间：
2018-09
影响因子：
5.3
通讯作者：
Jian Z
中科院分区：
文献类型：
--
作者：
Zhang Q;Cui T;Chang Y;Zhang W;Li S;He Y;Li B;Liu L;Wang G;Gao T;Li C;Jian Z
在白癜风中，皮肤色素脱失伴随着靶向黑素细胞的T细胞溶细胞活性增加，表明自身免疫耐受被破坏。已有研究表明，白癜风患者的自身免疫不耐受可能与TdR的量和功能受到抑制有关，但结论仍存在争议，其机制尚不清楚。在这项研究中，我们探讨了白癜风患者Treg反应受损的分子和细胞改变。我们的研究结果表明，活动期白癜风患者外周血中THBG的量急剧减少。此外，TGFAP的免疫调节功能减弱，CTLA 4、IL-10和TGF-β的表达降低。此外，白癜风患者血清中HO-1的表达降低，HO-1是TlR的功能性调节剂，HO-1代谢产物，包括胆红素、CoHb和铁的浓度也相应降低。此外，我们用血红素（一种HO-1激动剂）治疗白癜风患者的TcR，发现HO-1表达增强通过上调IL-10表达恢复了TcR的功能。我们的研究证明了HO-1在白癜风中受损的Treg反应中的重要作用，并表明HO-1作为白癜风治疗靶点的潜力。
In vitiligo, cutaneous depigmentation is accompanied by increased T cell cytolytic activity targeting melanocytes, indicating that autoimmune tolerance is disrupted. The inhibited amount and function of Tregs have been indicated to be involved in the autoimmune intolerance in vitiligo, however, with the conclusion still controversial and the involved mechanism unknown. In this study, we explored the molecular and cellular alterations accounting for the impaired Treg response in vitiligo. Our results showed that the amount of Tregs was drastically reduced in peripheral blood of active vitiligo patients. Furthermore, the immunoregulatory function of Tregs was attenuated, with lower expression of CTLA4, IL‐10 and TGF‐β. Moreover, the expression of HO‐1, a functional modulator of Tregs, was decreased in vitiligo Tregs, and the concentrations of HO‐1 metabolites, including bilirubin, CoHb and iron, were correspondingly decreased in serum of vitiligo patients. In addition, we treated the Tregs from vitiligo patients with Hemin, an agonist of HO‐1, and found that enhanced HO‐1 expression restored the function of Tregs by up‐regulating IL‐10 expression. Our study demonstrates the essential role of HO‐1 in the impaired Treg response in vitiligo and indicates the potential of HO‐1 as a therapeutic target in vitiligo management.
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