| Autor: |
Zheng, Handong, Wu, Xiang, Wu, Dandan, Jiang, Ruo-Lan, Castillo, Eliseo F., Chock, Cameron J., Zhou, Qin, Liu, Meilian, Dong, Chen, Yang, Xuexian O. |
| Zdroj: |
Mucosal Immunology; March 2020, Vol. 13 Issue: 2 p293-302, 10p |
| Abstrakt: |
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, Irf4and Il4, and excessive interleukin-4–signal transducer and activator of transcription 6 (IL-4−STAT6) signals resulted in repressive chromatin modification in the Foxp3locus and permissive modification in the Il4loci. 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. |
| Databáze: |
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