Bach2 overexpression represses Th9 cell differentiation by suppressing IRF4 expression in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by abnormal activation of T cells and caused by an imbalance in the production and clearance of apoptotic cells. We previously showed that the transcription regulator Bach2 regulated abnormal B‐cell activation in SLE. H...

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Main Authors: Yujun Sheng, Jiali Zhang, Keke Li, Hongyan Wang, Wenjun Wang, Leilei Wen, Jinping Gao, Xianfa Tang, Huayang Tang, He Huang, Minglong Cai, Tao Yuan, Lu Liu, Xiaodong Zheng, Zhengwei Zhu, Yong Cui
Format: Article
Language:English
Published: Wiley 2021-02-01
Series:FEBS Open Bio
Subjects:
Online Access:https://doi.org/10.1002/2211-5463.13050
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author Yujun Sheng
Jiali Zhang
Keke Li
Hongyan Wang
Wenjun Wang
Leilei Wen
Jinping Gao
Xianfa Tang
Huayang Tang
He Huang
Minglong Cai
Tao Yuan
Lu Liu
Xiaodong Zheng
Zhengwei Zhu
Yong Cui
author_facet Yujun Sheng
Jiali Zhang
Keke Li
Hongyan Wang
Wenjun Wang
Leilei Wen
Jinping Gao
Xianfa Tang
Huayang Tang
He Huang
Minglong Cai
Tao Yuan
Lu Liu
Xiaodong Zheng
Zhengwei Zhu
Yong Cui
author_sort Yujun Sheng
collection DOAJ
description Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by abnormal activation of T cells and caused by an imbalance in the production and clearance of apoptotic cells. We previously showed that the transcription regulator Bach2 regulated abnormal B‐cell activation in SLE. Here, we investigated whether Bach2 was also involved in Th9 cell differentiation in SLE. We found that the proportion of Th9 cells was enhanced in the peripheral blood mononuclear cells (PBMC) of SLE patients. The PBMC and CD4+ T cells of SLE patients exhibited a decrease of Bach2 expression and an increase of IL‐9 expression. Furthermore, Bach2 overexpression significantly repressed the levels of PU.1, IRF4, IL‐9, and Th9 cells in the CD4+ T cells of SLE patients and healthy volunteers. In addition, Bach2 overexpression inhibited the levels of IL‐9 and Th9 cells, whereas IRF4 upregulation enhanced the levels of IRF4 and IL‐9 and Th9 cells in the CD4+ T cells of SLE patients and healthy volunteers. The effect of IRF4 up‐regulation was abolished by Bach2 overexpression. In summary, our work suggests that Bach2 overexpression represses Th9 cell differentiation by suppressing IRF4 expression in SLE, and thus, Bach2 may be a novel potential target for SLE treatment.
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spelling doaj.art-2143e338bf8040c5978eaf4f37243b3b2022-12-22T04:41:01ZengWileyFEBS Open Bio2211-54632021-02-0111239540310.1002/2211-5463.13050Bach2 overexpression represses Th9 cell differentiation by suppressing IRF4 expression in systemic lupus erythematosusYujun Sheng0Jiali Zhang1Keke Li2Hongyan Wang3Wenjun Wang4Leilei Wen5Jinping Gao6Xianfa Tang7Huayang Tang8He Huang9Minglong Cai10Tao Yuan11Lu Liu12Xiaodong Zheng13Zhengwei Zhu14Yong Cui15Department of Dermatology Institute of Dermatology the First Affiliated Hospital Anhui Medical University Hefei ChinaDepartment of Dermatology Institute of Dermatology the First Affiliated Hospital Anhui Medical University Hefei ChinaDepartment of Dermatology China–Japan Friendship Hospital Beijing ChinaDepartment of Dermatology Institute of Dermatology the First Affiliated Hospital Anhui Medical University Hefei ChinaDepartment of Dermatology Institute of Dermatology the First Affiliated Hospital Anhui Medical University Hefei ChinaDepartment of Dermatology Institute of Dermatology the First Affiliated Hospital Anhui Medical University Hefei ChinaDepartment of Dermatology Institute of Dermatology the First Affiliated Hospital Anhui Medical University Hefei ChinaDepartment of Dermatology Institute of Dermatology the First Affiliated Hospital Anhui Medical University Hefei ChinaDepartment of Dermatology Institute of Dermatology the First Affiliated Hospital Anhui Medical University Hefei ChinaDepartment of Dermatology Institute of Dermatology the First Affiliated Hospital Anhui Medical University Hefei ChinaDepartment of Dermatology Institute of Dermatology the First Affiliated Hospital Anhui Medical University Hefei ChinaDepartment of Dermatology Institute of Dermatology the First Affiliated Hospital Anhui Medical University Hefei ChinaDepartment of Dermatology Institute of Dermatology the First Affiliated Hospital Anhui Medical University Hefei ChinaDepartment of Dermatology Institute of Dermatology the First Affiliated Hospital Anhui Medical University Hefei ChinaDepartment of Dermatology Institute of Dermatology the First Affiliated Hospital Anhui Medical University Hefei ChinaDepartment of Dermatology China–Japan Friendship Hospital Beijing ChinaSystemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by abnormal activation of T cells and caused by an imbalance in the production and clearance of apoptotic cells. We previously showed that the transcription regulator Bach2 regulated abnormal B‐cell activation in SLE. Here, we investigated whether Bach2 was also involved in Th9 cell differentiation in SLE. We found that the proportion of Th9 cells was enhanced in the peripheral blood mononuclear cells (PBMC) of SLE patients. The PBMC and CD4+ T cells of SLE patients exhibited a decrease of Bach2 expression and an increase of IL‐9 expression. Furthermore, Bach2 overexpression significantly repressed the levels of PU.1, IRF4, IL‐9, and Th9 cells in the CD4+ T cells of SLE patients and healthy volunteers. In addition, Bach2 overexpression inhibited the levels of IL‐9 and Th9 cells, whereas IRF4 upregulation enhanced the levels of IRF4 and IL‐9 and Th9 cells in the CD4+ T cells of SLE patients and healthy volunteers. The effect of IRF4 up‐regulation was abolished by Bach2 overexpression. In summary, our work suggests that Bach2 overexpression represses Th9 cell differentiation by suppressing IRF4 expression in SLE, and thus, Bach2 may be a novel potential target for SLE treatment.https://doi.org/10.1002/2211-5463.13050Bach2CD4+ T cellsIL‐9systemic lupus erythematosusTh9 cells
spellingShingle Yujun Sheng
Jiali Zhang
Keke Li
Hongyan Wang
Wenjun Wang
Leilei Wen
Jinping Gao
Xianfa Tang
Huayang Tang
He Huang
Minglong Cai
Tao Yuan
Lu Liu
Xiaodong Zheng
Zhengwei Zhu
Yong Cui
Bach2 overexpression represses Th9 cell differentiation by suppressing IRF4 expression in systemic lupus erythematosus
FEBS Open Bio
Bach2
CD4+ T cells
IL‐9
systemic lupus erythematosus
Th9 cells
title Bach2 overexpression represses Th9 cell differentiation by suppressing IRF4 expression in systemic lupus erythematosus
title_full Bach2 overexpression represses Th9 cell differentiation by suppressing IRF4 expression in systemic lupus erythematosus
title_fullStr Bach2 overexpression represses Th9 cell differentiation by suppressing IRF4 expression in systemic lupus erythematosus
title_full_unstemmed Bach2 overexpression represses Th9 cell differentiation by suppressing IRF4 expression in systemic lupus erythematosus
title_short Bach2 overexpression represses Th9 cell differentiation by suppressing IRF4 expression in systemic lupus erythematosus
title_sort bach2 overexpression represses th9 cell differentiation by suppressing irf4 expression in systemic lupus erythematosus
topic Bach2
CD4+ T cells
IL‐9
systemic lupus erythematosus
Th9 cells
url https://doi.org/10.1002/2211-5463.13050
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