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BCL-6 and EZH2 cooperate to epigenetically repress anti-inflammatory miR-142-3p/5p in lupus CD4+T cells

Cellular & Molecular Immunology volume 18, pages 504–505 (2021)Cite this article

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Epigenetics plays an important role in the pathogenesis of several autoimmune diseases.1,2,3 Indeed, a large body of evidence implicates abnormal T cell DNA methylation patterns in the pathogenies of lupus, a prototypical autoimmune systemic disease.4,5 Specific DNA methylation marks have been associated with clinical subsets of lupus patients,6,7,8 while others, such as methylation levels in apoptosis genes, might explain differences in disease susceptibility between ethnicities.9 Furthermore, demethylation of the IFI44L gene locus has recently been described as a novel promising highly sensitive and specific diagnostic tool in lupus.10

Recent work has suggested that early epigenetic changes in naĂŻve CD4+T cells are associated with disease flares in lupus patients. A proinflammatory epigenetic shift in naĂŻve CD4+T cells, preceding gene expression changes, primes naĂŻve CD4+T cells for Th2/Th17/Tfh differentiation, and opposes inhibitory Treg pathways as the disease becomes more active.11 The key Tfh transcription factor BCL-6 is progressively demethylated as the disease becomes more active in lupus patients.11 This proinflammatory epigenetic shift may be associated with disease flares and is induced by overexpression of the epigenetic modulator EZH2.11 EZH2 is a component of the polycomb repressive complex 2 (PRC2) and mediates trimethylation of histone H3 at lysine 27 (H3K27me3), a repressive epigenetic mark. Both in vitro and in vivo studies support a pathogenic role for EZH2 in lupus.12,13

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Authors and Affiliations

  1. Division of Rheumatology, Department of Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA

    Amr H. Sawalha

  2. Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Amr H. Sawalha

  3. Lupus Center of Excellence, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Amr H. Sawalha

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  1. Amr H. Sawalha
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Correspondence to Amr H. Sawalha.

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Sawalha, A.H. BCL-6 and EZH2 cooperate to epigenetically repress anti-inflammatory miR-142-3p/5p in lupus CD4+T cells. Cell Mol Immunol 18, 504–505 (2021). https://doi.org/10.1038/s41423-019-0288-z

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