Downregulation of miR-4772-3p promotes enhanced regulatory T cell capacity in malignant pleural effusion by elevating Helios levels

Yu, Wenqing; Ji, Ningfei; Gu, Changjiang; Sun, Zhixiao; Wang, Zhengxia; Chen, Zhongqi; Ma, Yuan; Wu, Zhenzhen; Wang, Yanli; Wu, Chaojie; Ding, Mingdong; Dai, Guihong; Yao, Juan; Jin, Renshun; Huang, Mao; Zhang, Mingshun

doi:10.1097/cm9.0000000000000517

Cited by 8 publications

(8 citation statements)

References 50 publications

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“…All specimens were processed as previously described. 19 The harvested PBMCs and PEMCs were washed twice with PBS and counted for subsequent detection.…”

Section: Methodsmentioning

confidence: 99%

IRF4 is Correlated with the Conversion to a Th17-Like Phenotype in Regulatory T Cells from the Malignant Pleural Effusion

Yu¹,

Ji²,

Gu³

et al. 2021

IJGM

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Background RORγt + Foxp3 + (Th17-like) Tregs are a plastic Treg subset implicated in immune-related diseases; however, the mechanism of Treg phenotypic transformation in malignant pleural effusion (MPE) has not been elucidated. Methods The percentage of CD4 + CD25 + Foxp3 + Helios + and RORγt + Foxp3 + Tregs from peripheral blood and pleural effusion mononuclear cells were measured. The level of interferon regulatory factor 4 (IRF4) mRNA expression was detected by quantitative real-time reverse transcription polymerase chain reaction. The effects of IRF4 on the induction of Tregs from patients with non-small cell lung cancer (NSCLC) were evaluated in vitro. Correlation assays between IRF4 expression and the frequency of RORγt + Foxp3 + Tregs were performed. Results The frequency of CD4 + CD25 + Foxp3 + Helios + Tregs and CD4 + RORγt + Th17 cells was both increased in the MPE of NSCLC patients. The group of double-positive Foxp3 + RORγt + Treg phenotype were identified in the pleural effusion. A significant increase in the frequency of Foxp3 + RORγt + Tregs was found in MPE compared with the non-malignant pleural effusion (NPE). Compared to NPE, the relative level of IRF4 expression was increased in the MPE. IRF4 expression was positively associated with the frequency of Foxp3 + RORγt + Tregs in the PE. In vitro, the level of Helios mRNA and protein expression was reduced in induced Tregs following IRF4 over-expression. Additionally, the level of RORγt protein expression was substantially increased. However, ectopic Helios expression in induced Tregs reversed the effects induced by enhanced IRF4 expression. Conclusion IRF4 may serve as a potential molecule that promotes the conversion of regulatory T cells from MPE to a Th17-like phenotype by modulating Helios.

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“…All specimens were processed as previously described. 19 The harvested PBMCs and PEMCs were washed twice with PBS and counted for subsequent detection.…”

Section: Methodsmentioning

confidence: 99%

IRF4 is Correlated with the Conversion to a Th17-Like Phenotype in Regulatory T Cells from the Malignant Pleural Effusion

Yu¹,

Ji²,

Gu³

et al. 2021

IJGM

Self Cite

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“…All specimens were processed as previously described. [23] The harvested PBMCs and PEMCs were washed twice with PBS and counted for subsequent detection.…”

Section: Sample Processingmentioning

confidence: 99%

IRF4 is Correlated With the Conversion to a Th17-like Phenotype in Regulatory T Cells From the Malignant Pleural Effusion

et al. 2021

Preprint

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Background: RORγt+Foxp3+ (Th17-like) Tregs are a plastic Treg subset implicated in immune-related diseases; however, the mechanism of Treg phenotypic transformation in malignant pleural effusion (MPE) has not been elucidated.Methods: The percentage of CD4+CD25+Foxp3+Helios+ and RORγt+Foxp3+ Tregs from peripheral blood and pleural effusion mononuclear cells were measured. The level of interferon regulatory factor 4 (IRF4) mRNA expression was detected by quantitative real-time reverse transcription polymerase chain reaction. The effects of IRF4 on the induction of Tregs from patients with non-small cell lung cancer (NSCLC) were evaluated in vitro. Correlation assays between IRF4 expression and the frequency of RORγt+Foxp3+ Tregs were performed. Results: The frequency of CD4+CD25+Foxp3+Helios+ Tregs and CD4+RORγt+ Th17 cells were both increased in the MPE of NSCLC patients. The group of double-positive Foxp3+RORγt+ Treg phenotype were identified in the pleural effusion. A significant increase in the frequency of Foxp3+RORγt+ Tregs was found in MPE compared with the non-malignant pleural effusion (NPE). Compared to NPE, the relative level of IRF4 expression was increased in the MPE. IRF4 expression was positively associated with the frequency of Foxp3+RORγt+ Tregs in the PE. In vitro, the level of Helios mRNA and protein expression was reduced in induced Tregs following IRF4 over-expression. Additionally, the level of RORγt protein expression was substantially increased. However, ectopic Helios expression in induced Tregs reversed the effects induced by enhanced IRF4 expression.Conclusion: IRF4 may serve as a potential molecule that promotes the conversion of regulatory T cells from MPE to a Th17-like phenotype by modulating Helios.

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“…Furthermore, Helios was found to be expressed in acute myeloid leukemia (AML) cells, and its depletion in AML cells resulted in decreased colony formation and slowed down oncogenesis ( Park et al, 2019 ). The elevating Helios levels are related to the capacity of Tregs in malignant pleural effusion due to the downregulation of miR-4772-3p ( Yu et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Ikaros Proteins in Tumor: Current Perspectives and New Developments

Xia

Yuan

Han

et al. 2021

Front. Mol. Biosci.

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Ikaros is a zinc finger transcription factor (TF) of the Krüppel family member, which significantly regulates normal lymphopoiesis and tumorigenesis. Ikaros can directly initiate or suppress tumor suppressors or oncogenes, consequently regulating the survival and proliferation of cancer cells. Over recent decades, a series of studies have been devoted to exploring and clarifying the relationship between Ikaros and associated tumors. Therapeutic strategies targeting Ikaros have shown promising therapeutic effects in both pre-clinical and clinical trials. Nevertheless, the increasingly prominent problem of drug resistance targeted to Ikaros and its analog is gradually appearing in our field of vision. This article reviews the role of Ikaros in tumorigenesis, the mechanism of drug resistance, the progress of targeting Ikaros in both pre-clinical and clinical trials, and the potential use of associated therapy in cancer therapy.

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Downregulation of miR-4772-3p promotes enhanced regulatory T cell capacity in malignant pleural effusion by elevating Helios levels

Cited by 8 publications

References 50 publications

IRF4 is Correlated with the Conversion to a Th17-Like Phenotype in Regulatory T Cells from the Malignant Pleural Effusion

IRF4 is Correlated with the Conversion to a Th17-Like Phenotype in Regulatory T Cells from the Malignant Pleural Effusion

IRF4 is Correlated With the Conversion to a Th17-like Phenotype in Regulatory T Cells From the Malignant Pleural Effusion

Ikaros Proteins in Tumor: Current Perspectives and New Developments

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