IRF4 is Correlated with the Conversion to a Th17-Like Phenotype in Regulatory T Cells from the Malignant Pleural Effusion
Wenqing Yu,1,* Ningfei Ji,2,* Chengjing Gu,3,* Juan Yao,4 Mingdong Ding,1 Daming Zhou,1 Mao Huang,2 Mingshun Zhang5,6 1Department of Infectious Diseases, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu, 225300, People’s Republic of China; 2Departm...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2021-09-01
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| Series: | International Journal of General Medicine |
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| Online Access: | https://www.dovepress.com/irf4-is-correlated-with-the-conversion-to-a-th17-like-phenotype-in-reg-peer-reviewed-fulltext-article-IJGM |
| _version_ | 1818367204137107456 |
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| author | Yu W Ji N Gu C Yao J Ding M Zhou D Huang M Zhang M |
| author_facet | Yu W Ji N Gu C Yao J Ding M Zhou D Huang M Zhang M |
| author_sort | Yu W |
| collection | DOAJ |
| description | Wenqing Yu,1,* Ningfei Ji,2,* Chengjing Gu,3,* Juan Yao,4 Mingdong Ding,1 Daming Zhou,1 Mao Huang,2 Mingshun Zhang5,6 1Department of Infectious Diseases, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu, 225300, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 3Department of Pharmacy, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu, 225300, People’s Republic of China; 4Department of Oncology, Huaian Hospital of Huaian City, Huaian, Jiangsu, 223200, People’s Republic of China; 5Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu, 211166, People’s Republic of China; 6NHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, Jiangsu, 211166, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chengjing GuDepartment of Pharmacy, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu, 225300, People’s Republic of ChinaTel +86 0523-86606290Email chengjingyu706@163.comWenqing YuDepartment of Infectious Diseases, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu, 225300, People’s Republic of ChinaEmail wenqinggu706@126.comBackground: 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.Keywords: malignant pleural effusion, lung cancer, IRF4, regulatory T cells, phenotypic transformation |
| first_indexed | 2024-12-13T22:48:20Z |
| format | Article |
| id | doaj.art-fad85cd214fd471193abfbfdc7ce6a7e |
| institution | Directory Open Access Journal |
| issn | 1178-7074 |
| language | English |
| last_indexed | 2024-12-13T22:48:20Z |
| publishDate | 2021-09-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of General Medicine |
| spelling | doaj.art-fad85cd214fd471193abfbfdc7ce6a7e2022-12-21T23:28:40ZengDove Medical PressInternational Journal of General Medicine1178-70742021-09-01Volume 146009601969130IRF4 is Correlated with the Conversion to a Th17-Like Phenotype in Regulatory T Cells from the Malignant Pleural EffusionYu WJi NGu CYao JDing MZhou DHuang MZhang MWenqing Yu,1,* Ningfei Ji,2,* Chengjing Gu,3,* Juan Yao,4 Mingdong Ding,1 Daming Zhou,1 Mao Huang,2 Mingshun Zhang5,6 1Department of Infectious Diseases, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu, 225300, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 3Department of Pharmacy, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu, 225300, People’s Republic of China; 4Department of Oncology, Huaian Hospital of Huaian City, Huaian, Jiangsu, 223200, People’s Republic of China; 5Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu, 211166, People’s Republic of China; 6NHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, Jiangsu, 211166, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chengjing GuDepartment of Pharmacy, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu, 225300, People’s Republic of ChinaTel +86 0523-86606290Email chengjingyu706@163.comWenqing YuDepartment of Infectious Diseases, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu, 225300, People’s Republic of ChinaEmail wenqinggu706@126.comBackground: 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.Keywords: malignant pleural effusion, lung cancer, IRF4, regulatory T cells, phenotypic transformationhttps://www.dovepress.com/irf4-is-correlated-with-the-conversion-to-a-th17-like-phenotype-in-reg-peer-reviewed-fulltext-article-IJGMmalignant pleural effusionlung cancerirf4regulatory t cellsphenotypic transformation |
| spellingShingle | Yu W Ji N Gu C Yao J Ding M Zhou D Huang M Zhang M IRF4 is Correlated with the Conversion to a Th17-Like Phenotype in Regulatory T Cells from the Malignant Pleural Effusion International Journal of General Medicine malignant pleural effusion lung cancer irf4 regulatory t cells phenotypic transformation |
| title | IRF4 is Correlated with the Conversion to a Th17-Like Phenotype in Regulatory T Cells from the Malignant Pleural Effusion |
| title_full | IRF4 is Correlated with the Conversion to a Th17-Like Phenotype in Regulatory T Cells from the Malignant Pleural Effusion |
| title_fullStr | IRF4 is Correlated with the Conversion to a Th17-Like Phenotype in Regulatory T Cells from the Malignant Pleural Effusion |
| title_full_unstemmed | IRF4 is Correlated with the Conversion to a Th17-Like Phenotype in Regulatory T Cells from the Malignant Pleural Effusion |
| title_short | IRF4 is Correlated with the Conversion to a Th17-Like Phenotype in Regulatory T Cells from the Malignant Pleural Effusion |
| title_sort | irf4 is correlated with the conversion to a th17 like phenotype in regulatory t cells from the malignant pleural effusion |
| topic | malignant pleural effusion lung cancer irf4 regulatory t cells phenotypic transformation |
| url | https://www.dovepress.com/irf4-is-correlated-with-the-conversion-to-a-th17-like-phenotype-in-reg-peer-reviewed-fulltext-article-IJGM |
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