Treg expression of CIS suppresses allergic airway inflammation through antagonizing an autonomous TH2 program.,Mucosal Immunology

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Treg expression of CIS suppresses allergic airway inflammation through antagonizing an autonomous TH2 program.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2019-11-28 , DOI: 10.1038/s41385-019-0236-3
Handong Zheng ₁ , Xiang Wu _{1,

2} , Dandan Wu _{1,

3,

4} , Ruo-Lan Jiang _{1,

2} , Eliseo F Castillo ₅ , Cameron J Chock ₁ , Qin Zhou _{1,

3} , Meilian Liu ₃ , Chen Dong ₆ , Xuexian O Yang ₁

Affiliation

Maintenance of regulatory T (Treg) cells is crucial for the regulatory function of Treg cells in immune homeostasis and self-tolerance; however, the detailed underlying mechanisms remain elusive. In the current study, we found that the cytokine suppressor CIS (cytokine induced SH-2 protein) is required for maintenance of Treg cell identity. Mice with Treg-specific Cis-deficiency displayed aggravated experimental allergic asthma, and in adulthood, developed splenomegaly, lymphadenopathy and spontaneous eosinophilic airway inflammation, accompanied by accumulation of effector memory helper T (TH) cells. Cis-deficiency led to the loss of Foxp3 expression and the decrease in suppressive function of Treg cells. Cis-deficient Treg cells expressed TH2 cell signature genes, Gata3, Irf4 and Il4, and excessive interleukin-4-signal transducer and activator of transcription 6 (IL-4-STAT6) signals resulted in repressive chromatin modification in the Foxp3 locus and permissive modification in the Il4 loci. In vitro, blockade of IL-4 restored the expression of Foxp3 and the suppressive function of inducible Treg (iTreg) cells. Thus, we identified a novel feedback loop in stabilization of Treg cells and suppression of TH2-type inflammation in a Treg-intrinsic manner.

中文翻译：

CIS 的 Treg 表达通过拮抗自主 TH2 程序来抑制过敏性气道炎症。

调节性 T (Treg) 细胞的维持对于 Treg 细胞在免疫稳态和自我耐受中的调节功能至关重要；然而，详细的潜在机制仍然难以捉摸。在当前的研究中，我们发现细胞因子抑制因子 CIS（细胞因子诱导的 SH-2 蛋白）是维持 Treg 细胞特性所必需的。具有 Treg 特异性顺式缺陷的小鼠表现出加重的实验性过敏性哮喘，成年后出现脾肿大、淋巴结肿大和自发性嗜酸性粒细胞性气道炎症，并伴有效应记忆辅助 T (TH) 细胞的积累。顺式缺陷导致 Foxp3 表达的丧失和 Treg 细胞抑制功能的降低。顺式缺陷型 Treg 细胞表达 TH2 细胞特征基因 Gata3、Irf4 和 Il4，过多的白细胞介素 4 信号转导和转录激活因子 6 (IL-4-STAT6) 信号导致 Foxp3 基因座的抑制性染色质修饰和 Il4 基因座的允许性修饰。在体外，IL-4 的阻断恢复了 Foxp3 的表达和诱导型 Treg (iTreg) 细胞的抑制功能。因此，我们确定了一个新的反馈回路，以稳定 Treg 细胞和以 Treg 固有方式抑制 TH2 型炎症。

更新日期：2019-11-28

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