BACH2 regulates the function of human CD4+CD45RA−Foxp3l° cytokine‐secreting T cells and promotes B‐cell response in systemic lupus erythematosus

Zheng, Yingxia; Lu, Yiwen; Huang, Xinfang; Liang, Han; Chen, Zheyi; Zhou, Bingqian; Ma, Yonggang; Xie, Guohua; Yang, Junyao; Bian, Bingxian; Li, Li; Nie, Hong; Pan, Xiaohong; Shen, Lisong

doi:10.1002/eji.201948320

Cited by 9 publications

(5 citation statements)

References 40 publications

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“…On the other hand, IL-9 negatively regulates virus-mediated inflammation and enhances the immunosuppressive activity of natural Treg, thus Bach2 has reported to be associated with the terminal differentiation and maturation of both B and T lymphocytes [22]. Bach2 takes part in the development of SLE by regulating the immune functions of B and T lymphocytes [23,24]. However, whether Bach2 can regulate Th9 cell differentiation in SLE is still unclear.…”

Section: Discussionmentioning

confidence: 99%

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

Sheng

Zhang

et al. 2020

FEBS Open Bio

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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 regulates abnormal B cell activation in SLE. Here, we investigated whether Bach2 is 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 up-regulation 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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Section: Discussionmentioning

confidence: 99%

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

Sheng

Zhang

et al. 2020

FEBS Open Bio

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“…III cells) is elevated in active SLE patients and that the Bach2 level in Fr. III cells is negatively correlated with the SLEDAI [18]. Forced transcription of Bach2 in Fr.…”

Section: Discussionmentioning

confidence: 99%

“…Forced transcription of Bach2 in Fr. III cells resulted in decreased cytokine levels and inhibited B‐cell responses [18]. This suggests that the high expression of Bach2 in T‐cell subsets helps to alleviate the SLEDAI and reduce the production of cytokines.…”

Section: Discussionmentioning

confidence: 99%

“…In Bach2-deficient cells, 31.8% of upregulated genes are associated with effector lineages gene transcripts involved in the process by which naïve cells differentiate into Th1, Th2, or Th17 cells [11]. Increasing genomic and clinical evidence has linked Bach2 to autoimmune diseases, such as SLE [14,17,18]. In autoimmune diseases, pathogenic Th cells act as triggers, while B cells act as bullets.…”

Section: Introductionmentioning

confidence: 99%

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Bach2 in CD4⁺ T cells from SLE patients modulates B‐cell differentiation and IgG production

Long

Yang

et al. 2023

Eur J Immunol

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T and B cells participate in the development of systemic lupus erythematosus (SLE). BTB and CNC homology 2 (Bach2) is an irreplaceable regulator in the T and B lineages that helps to maintain immune homeostasis. However, the function of Bach2 in the pathogenesis of SLE has not been studied in depth. Flow cytometry and qRT‒PCR were used to assess Bach2 levels, bisulfite sequencing PCR was used to measure the methylation level, and silencing by electroporation and stimulation with a cytokine concentration gradient were used to investigate the effect of Bach2 on T cells. Bach2 expression was elevated in the helper T‐cell subsets (T follicular helper, Th1, Th2, Th17, and Treg cells) of SLE patients and negatively correlated with disease severity and autoantibody levels. CD4+ T cells from SLE patients had decreased methylation levels in the Bach2 promoter region. Silencing Bach2 in CD4+ T cells induced increases in the CD19+ B‐cell count, plasmablasts, and secretion of IgG by prompting the secretion of cytokines. The activation signals CD3/CD28, IL‐6, and IL‐21 upregulated Bach2 expression in CD4+ T cells. The regulation of Bach2 by cytokines and T‐cell activation signals in CD4+ T cells was shown to act on B cells and play a protective role against SLE.

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“…It seems its role is dynamic in the status of CD4 T cells. The differential expression of BACH2 in CD4 T cells from UCB versus AB controls IL-2 production in CD4 T cells [ 44 ], regulates IL-2 receptor signaling in Tregs [ 45 ], and plays a key role in regulating Treg functions [ 46 ]. Intriguingly, UCB iTregs exhibit more robust, sustained FOXP3 expression and enhanced stability compared with AB iTregs.…”

Section: Bach2 Cell Type-specific Rolesmentioning

confidence: 99%

BACH2: The Future of Induced T-Regulatory Cell Therapies

Zwick,

Vo,

Shim

et al. 2024

Cells

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BACH2 (BTB Domain and CNC Homolog 2) is a transcription factor that serves as a central regulator of immune cell differentiation and function, particularly in T and B lymphocytes. A picture is emerging that BACH2 may function as a master regulator of cell fate that is exquisitely sensitive to cell activation status. In particular, BACH2 plays a key role in stabilizing the phenotype and suppressive function of transforming growth factor-beta (TGF-β)-derived human forkhead box protein P3 (FOXP3)+ inducible regulatory T cells (iTregs), a cell type that holds great clinical potential as a cell therapeutic for diverse inflammatory conditions. As such, BACH2 potentially could be targeted to overcome the instability of the iTreg phenotype and suppressive function that has hampered their clinical application. In this review, we focus on the role of BACH2 in T cell fate and iTreg function and stability. We suggest approaches to modulate BACH2 function that may lead to more stable and efficacious Treg cell therapies.

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BACH2 regulates the function of human CD4⁺CD45RA⁻Foxp3^l° cytokine‐secreting T cells and promotes B‐cell response in systemic lupus erythematosus

Cited by 9 publications

References 40 publications

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

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

Bach2 in CD4⁺ T cells from SLE patients modulates B‐cell differentiation and IgG production

BACH2: The Future of Induced T-Regulatory Cell Therapies

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BACH2 regulates the function of human CD4+CD45RA−Foxp3l° cytokine‐secreting T cells and promotes B‐cell response in systemic lupus erythematosus

Cited by 9 publications

References 40 publications

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

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

Bach2 in CD4+ T cells from SLE patients modulates B‐cell differentiation and IgG production

BACH2: The Future of Induced T-Regulatory Cell Therapies

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BACH2 regulates the function of human CD4⁺CD45RA⁻Foxp3^l° cytokine‐secreting T cells and promotes B‐cell response in systemic lupus erythematosus

Bach2 in CD4⁺ T cells from SLE patients modulates B‐cell differentiation and IgG production