Helios expression in regulatory T cells promotes immunosuppression, angiogenesis and the growth of leukemia cells in pediatric acute lymphoblastic leukemia. (April 2018)

• Record Type: Journal Article
• Authors: Li, Xue; Li, Dong; Huang, Xiaoyang; Zhou, Panpan; Shi, Qing; Zhang, Bing; Ju, Xiuli
• Is Part Of: Leukemia research. Volume 67(2018)
• Page Start: 60
• Page End: 66
• Publication Date: 2018-04
• Subjects: Acute lymphoblastic leukemia -- Regulatory T cells -- Helios -- Angiogenesis -- Apoptosis; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2018.02.007
• Languages: English
• ISSNs: 0145-2126

Abstract

Highlights: Helios expression in Tregs participates in a variety of biological processes in pediatric ALL. Helios + Tregs increase in pre-B ALL and define higher risk of ALL. Helios enhances the suppressive function of Tregs by regulating TGF-β1 production. Helios + Tregs regulate angiogenesis in pre-B ALL via the VEGFA/VEGFR2 pathway. Helios + Tregs control nalm-6 apoptosis by Bcl-2. Abstract: Regulatory T cells (Tregs) characterized by the transcription factor forkhead box P3 (FoxP3) are crucial for maintaining immune tolerance and preventing autoimmunity. However, FoxP3 does not function alone and Helios is considered a potential candidate for defining Treg subsets. In this study, we investigated the expression and function of Helios for identifying Tregs in childhood precursor B-cell acute lymphoblastic leukemia (pre-B ALL). Our results demonstrated that patients with pre-B ALL had a higher percentage of Helios + FoxP3 + CD4 + Tregs. And there was a positive correlation between the expression of Helios and the suppressive function of Tregs, the risk gradation of ALL. Helios in combination with CD4 and FoxP3 may be an effective way to detect functional Tregs in pre-B ALL by promoting the secretion of transforming growth factor (TGF)-β1. Furthermore, Helios + Tregs could regulate angiogenesis in the BM niche of pre-B ALL via the VEGFA/VEGFR2 pathway. We also found Helios + Tregs decreased apoptosis rate of nalm-6 cells by up-regulating the expression of anti-apoptosis protein Bcl-2. In summary, these data strongly imply the physiological importance of Helios expression in Tregs, and suggest that the manipulation of Helios may serve as a novel strategy for cancer immunotherapy.