Cargando…
Transcription Factor IRF4 Dysfunction Affects the Immunosuppressive Function of Treg Cells in Patients with Primary Immune Thrombocytopenia
BACKGROUND: Th17/Treg balance skews towards Th17 in ITP patient. IRF4 has been highlighted for its close relationship to the immunosuppressive function of Treg cells and the IL-17 synthesis in CD4(+) T cells. This study was aimed at examining the effects of IRF4 to the Th17/Treg cells in patients wi...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6652070/ https://www.ncbi.nlm.nih.gov/pubmed/31380412 http://dx.doi.org/10.1155/2019/1050285 |
_version_ | 1783438491620737024 |
---|---|
author | Tang, Meiwen Cheng, Luya Li, Feng Wu, Boting Chen, Pu Zhan, Yanxia Hua, Fanli Min, Zhihui Ke, Yang Liu, Chanjuan Yuan, Ling Sun, Lihua Chen, Hao Ji, Lili Cheng, Yunfeng |
author_facet | Tang, Meiwen Cheng, Luya Li, Feng Wu, Boting Chen, Pu Zhan, Yanxia Hua, Fanli Min, Zhihui Ke, Yang Liu, Chanjuan Yuan, Ling Sun, Lihua Chen, Hao Ji, Lili Cheng, Yunfeng |
author_sort | Tang, Meiwen |
collection | PubMed |
description | BACKGROUND: Th17/Treg balance skews towards Th17 in ITP patient. IRF4 has been highlighted for its close relationship to the immunosuppressive function of Treg cells and the IL-17 synthesis in CD4(+) T cells. This study was aimed at examining the effects of IRF4 to the Th17/Treg cells in patients with ITP. METHODS: Treg and Teff cells were isolated from PBMCs of newly diagnosed ITP patients. The percentages of CD4(+)CD25(hi)Foxp3(+)Treg cells and the CD3(+)CD4(+)IL-17(+)Th17 cells were detected by flow cytometry. After being cultured, the supernatants of Tregs were collected for IL-10 concentration test. The IRF4 levels of Tregs were measured. Teffs were cultured alone or with Tregs for 24 hours. Then the supernatants were collected for IL-17 concentration test. The binding intensity of IRF4 to the gene IL-10 in Treg cells was detected by ChIP-qPCR. Metabolic assays for Teffs and Tregs were performed with Agilent Seahorse XF96 Analyzer. RESULTS: The secretion of IL-10 by Tregs was decreased in ITP patients. The intensity of IRF4 binding to IL-10 DNA of Tregs in patients was higher than that of normal controls and Teffs in ITP patients. The expressions of IRF4 of Tregs in ITP patients were remarkably lower than that of healthy controls. The percentage of Th17 cells in healthy controls was significantly increased after IRF4 mRNA silencing. Abnormal metabolism of Treg and Teff cells was found in ITP patients. CONCLUSION: The skewed ratio of Th17/Treg cells and dysfunction of Treg cells in newly diagnosed ITP patients was at least partly caused by IRF4 dysfunction. The underlying mechanism might be the impact of IRF4 on the metabolism of Treg and Teff cells. |
format | Online Article Text |
id | pubmed-6652070 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-66520702019-08-04 Transcription Factor IRF4 Dysfunction Affects the Immunosuppressive Function of Treg Cells in Patients with Primary Immune Thrombocytopenia Tang, Meiwen Cheng, Luya Li, Feng Wu, Boting Chen, Pu Zhan, Yanxia Hua, Fanli Min, Zhihui Ke, Yang Liu, Chanjuan Yuan, Ling Sun, Lihua Chen, Hao Ji, Lili Cheng, Yunfeng Biomed Res Int Research Article BACKGROUND: Th17/Treg balance skews towards Th17 in ITP patient. IRF4 has been highlighted for its close relationship to the immunosuppressive function of Treg cells and the IL-17 synthesis in CD4(+) T cells. This study was aimed at examining the effects of IRF4 to the Th17/Treg cells in patients with ITP. METHODS: Treg and Teff cells were isolated from PBMCs of newly diagnosed ITP patients. The percentages of CD4(+)CD25(hi)Foxp3(+)Treg cells and the CD3(+)CD4(+)IL-17(+)Th17 cells were detected by flow cytometry. After being cultured, the supernatants of Tregs were collected for IL-10 concentration test. The IRF4 levels of Tregs were measured. Teffs were cultured alone or with Tregs for 24 hours. Then the supernatants were collected for IL-17 concentration test. The binding intensity of IRF4 to the gene IL-10 in Treg cells was detected by ChIP-qPCR. Metabolic assays for Teffs and Tregs were performed with Agilent Seahorse XF96 Analyzer. RESULTS: The secretion of IL-10 by Tregs was decreased in ITP patients. The intensity of IRF4 binding to IL-10 DNA of Tregs in patients was higher than that of normal controls and Teffs in ITP patients. The expressions of IRF4 of Tregs in ITP patients were remarkably lower than that of healthy controls. The percentage of Th17 cells in healthy controls was significantly increased after IRF4 mRNA silencing. Abnormal metabolism of Treg and Teff cells was found in ITP patients. CONCLUSION: The skewed ratio of Th17/Treg cells and dysfunction of Treg cells in newly diagnosed ITP patients was at least partly caused by IRF4 dysfunction. The underlying mechanism might be the impact of IRF4 on the metabolism of Treg and Teff cells. Hindawi 2019-07-10 /pmc/articles/PMC6652070/ /pubmed/31380412 http://dx.doi.org/10.1155/2019/1050285 Text en Copyright © 2019 Meiwen Tang et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Tang, Meiwen Cheng, Luya Li, Feng Wu, Boting Chen, Pu Zhan, Yanxia Hua, Fanli Min, Zhihui Ke, Yang Liu, Chanjuan Yuan, Ling Sun, Lihua Chen, Hao Ji, Lili Cheng, Yunfeng Transcription Factor IRF4 Dysfunction Affects the Immunosuppressive Function of Treg Cells in Patients with Primary Immune Thrombocytopenia |
title | Transcription Factor IRF4 Dysfunction Affects the Immunosuppressive Function of Treg Cells in Patients with Primary Immune Thrombocytopenia |
title_full | Transcription Factor IRF4 Dysfunction Affects the Immunosuppressive Function of Treg Cells in Patients with Primary Immune Thrombocytopenia |
title_fullStr | Transcription Factor IRF4 Dysfunction Affects the Immunosuppressive Function of Treg Cells in Patients with Primary Immune Thrombocytopenia |
title_full_unstemmed | Transcription Factor IRF4 Dysfunction Affects the Immunosuppressive Function of Treg Cells in Patients with Primary Immune Thrombocytopenia |
title_short | Transcription Factor IRF4 Dysfunction Affects the Immunosuppressive Function of Treg Cells in Patients with Primary Immune Thrombocytopenia |
title_sort | transcription factor irf4 dysfunction affects the immunosuppressive function of treg cells in patients with primary immune thrombocytopenia |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6652070/ https://www.ncbi.nlm.nih.gov/pubmed/31380412 http://dx.doi.org/10.1155/2019/1050285 |
work_keys_str_mv | AT tangmeiwen transcriptionfactorirf4dysfunctionaffectstheimmunosuppressivefunctionoftregcellsinpatientswithprimaryimmunethrombocytopenia AT chengluya transcriptionfactorirf4dysfunctionaffectstheimmunosuppressivefunctionoftregcellsinpatientswithprimaryimmunethrombocytopenia AT lifeng transcriptionfactorirf4dysfunctionaffectstheimmunosuppressivefunctionoftregcellsinpatientswithprimaryimmunethrombocytopenia AT wuboting transcriptionfactorirf4dysfunctionaffectstheimmunosuppressivefunctionoftregcellsinpatientswithprimaryimmunethrombocytopenia AT chenpu transcriptionfactorirf4dysfunctionaffectstheimmunosuppressivefunctionoftregcellsinpatientswithprimaryimmunethrombocytopenia AT zhanyanxia transcriptionfactorirf4dysfunctionaffectstheimmunosuppressivefunctionoftregcellsinpatientswithprimaryimmunethrombocytopenia AT huafanli transcriptionfactorirf4dysfunctionaffectstheimmunosuppressivefunctionoftregcellsinpatientswithprimaryimmunethrombocytopenia AT minzhihui transcriptionfactorirf4dysfunctionaffectstheimmunosuppressivefunctionoftregcellsinpatientswithprimaryimmunethrombocytopenia AT keyang transcriptionfactorirf4dysfunctionaffectstheimmunosuppressivefunctionoftregcellsinpatientswithprimaryimmunethrombocytopenia AT liuchanjuan transcriptionfactorirf4dysfunctionaffectstheimmunosuppressivefunctionoftregcellsinpatientswithprimaryimmunethrombocytopenia AT yuanling transcriptionfactorirf4dysfunctionaffectstheimmunosuppressivefunctionoftregcellsinpatientswithprimaryimmunethrombocytopenia AT sunlihua transcriptionfactorirf4dysfunctionaffectstheimmunosuppressivefunctionoftregcellsinpatientswithprimaryimmunethrombocytopenia AT chenhao transcriptionfactorirf4dysfunctionaffectstheimmunosuppressivefunctionoftregcellsinpatientswithprimaryimmunethrombocytopenia AT jilili transcriptionfactorirf4dysfunctionaffectstheimmunosuppressivefunctionoftregcellsinpatientswithprimaryimmunethrombocytopenia AT chengyunfeng transcriptionfactorirf4dysfunctionaffectstheimmunosuppressivefunctionoftregcellsinpatientswithprimaryimmunethrombocytopenia |