Entinostat, a histone deacetylase inhibitor, increases the population of IL-10<sup>+</sup>regulatory B cells to suppress contact hypersensitivity

Min, Keun Young; Lee, Min Bum; Lee, Dajeong; Jo, Min Geun; Lee, Ji Eon; Choi, Min Yeong; You, Jueng Soo; Kim, Young Mi; Park, Yeong Min; Kim, Hyuk Soon; Choi, Wahn Soo

doi:10.5483/bmbrep.2021.54.10.092

Cited by 6 publications

(4 citation statements)

References 35 publications

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“…Increased sensitization of cancer cells with decreased homologous recombination repair capacity has been observed upon HDAC inhibition in combination with antitumor drugs (18,(57)(58)(59). Specifically, inhibition of class I HDACs by high dosage of Entinostat (MS-275) induced γH2AX, significantly inhibited cellular growth and triggered apoptosis (60)(61)(62)(63).…”

Section: Dna Damage Does Not Impact Gse1-hdac1 Complex Deacetylase Ac...mentioning

confidence: 99%

GSE1 links the HDAC1/CoREST co-repressor complex to DNA damage

Vcelkova

Reiter

Zylka

et al. 2023

Preprint

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Post-translational modifications of histones are important regulators of the DNA damage response (DDR). By using affinity purification mass spectrometry (AP-MS) we discovered that genetic suppressor element 1 (GSE1) forms a complex with the HDAC1/CoREST deacetylase/demethylase co-repressor complex. In-depth phosphorylome analysis revealed that loss of GSE1 results in impaired DDR, ATR signalling and gamma H2AX formation upon DNA damage induction. Altered profiles of ATR target serine-glutamine motifs (SQ) on DDR-related hallmark proteins point to a defect in DNA damage sensing. In addition, GSE1 knock-out cells showed hampered DNA damage-induced phosphorylation on SQ motifs of regulators of histone post-translational modifications, suggesting altered histone modification. While loss of GSE1 does not affect the histone deacetylation activity of CoREST, GSE1 appears to be essential for binding of the deubiquitinase USP22 to CoREST and for the deubiquitination of H2B K120 in response to DNA damage. The combination of deacetylase, demethylase, and deubiquitinase activity makes the USP22-GSE1-CoREST subcomplex a multi enzymatic eraser that seems to play an important role during DDR. Since GSE1 has been previously associated with cancer progression and survival our findings are potentially of high medical relevance.

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Section: Dna Damage Does Not Impact Gse1-hdac1 Complex Deacetylase Ac...mentioning

confidence: 99%

GSE1 links the HDAC1/CoREST co-repressor complex to DNA damage

Vcelkova

Reiter

Zylka

et al. 2023

Preprint

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“…Inhibition of HDAC11 increases IL-10 production by B cells in patients with allergic rhinitis [ 119 ]. Entinostat, an HDAC inhibitor, inhibits the binding of HDAC1 to the promoter region of Il10 and promotes the induction of IL-10-producing B cells by LPS [ 120 ]. Another HDAC inhibitor, trichostatin A, increases the frequency of IL‑10- and TGF‑β‑producing CD5 + CD1d high B cells in vitro and in vivo [ 121 ], suggesting that HDAC inhibitors might be potential agents for treating autoimmune diseases and transplant rejection.…”

Section: Epigenetic Modifications Regulate B-cell Differentiationmentioning

confidence: 99%

Epigenetic regulation of B cells and its role in autoimmune pathogenesis

et al. 2022

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B cells play a pivotal role in the pathogenesis of autoimmune diseases. Although previous studies have shown many genetic polymorphisms associated with B-cell activation in patients with various autoimmune disorders, progress in epigenetic research has revealed new mechanisms leading to B-cell hyperactivation. Epigenetic mechanisms, including those involving histone modifications, DNA methylation, and noncoding RNAs, regulate B-cell responses, and their dysregulation can contribute to the pathogenesis of autoimmune diseases. Patients with autoimmune diseases show epigenetic alterations that lead to the initiation and perpetuation of autoimmune inflammation. Moreover, many clinical and animal model studies have shown the promising potential of epigenetic therapies for patients. In this review, we present an up-to-date overview of epigenetic mechanisms with a focus on their roles in regulating functional B-cell subsets. Furthermore, we discuss epigenetic dysregulation in B cells and highlight its contribution to the development of autoimmune diseases. Based on clinical and preclinical evidence, we discuss novel epigenetic biomarkers and therapies for patients with autoimmune disorders.

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“…Sodium butyrate restrains the activation of HDAC1 in the antigen specific B cells to induce the expression of IL-10 and decrease the production of IgE in allergic rhinitis model ( 51 ). Another HDAC inhibitor entinostat stimulates the formation of IL-10 positive Breg cells to suppress contact hypersensitivity in vivo ( 54 ). Indeed, the administration with Clostridium butyricum (C. butyricum) enforces the effect of specific immunotherapy on intestinal allergic inflammation by increasing the phosphorylation of HDAC1, the expression of IL-10 and the IgE-producing plasma cells ( 67 ).…”

Section: Regulation Of Inflammatory Cytokines and Downstream Protein ...mentioning

confidence: 99%

The emerging role of histone deacetylase 1 in allergic diseases

Wang

2022

Front. Immunol.

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Histone deacetylase 1 (HDAC1) is a unique member of the classes I HDACs and helps to regulate acute and chronic adaptation to environmental stimuli such as allergen, stress. Allergic diseases are complex diseases resulting from the effect of multiple genetic and interacting foreign substances. Epigenetics play an important role in both pathological and immunomodulatory conditions of allergic diseases. To be consistent with this role, recent evidence strongly suggests that histone deacetylase 1 (HDAC1) plays a critical role in allergic response. HDAC1 expression is stimulated by allergen and attributes to increase T helper 2 (Th2) cytokine levels, decrease Th1/Th17 cells and anti-inflammatory cytokine Interleukin-10 (IL-10), and TWIK-related potassium channel-1 (Trek-1) expression. This review focuses on the contribution of HDAC1 and the regulatory role in characterizing allergic endotypes with common molecular pathways and understanding allergic multimorbidity relationships, as well as addressing their potential as therapeutic targets for these conditions.

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Entinostat, a histone deacetylase inhibitor, increases the population of IL-10⁺regulatory B cells to suppress contact hypersensitivity

Cited by 6 publications

References 35 publications

GSE1 links the HDAC1/CoREST co-repressor complex to DNA damage

GSE1 links the HDAC1/CoREST co-repressor complex to DNA damage

Epigenetic regulation of B cells and its role in autoimmune pathogenesis

The emerging role of histone deacetylase 1 in allergic diseases

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Entinostat, a histone deacetylase inhibitor, increases the population of IL-10+regulatory B cells to suppress contact hypersensitivity

Cited by 6 publications

References 35 publications

GSE1 links the HDAC1/CoREST co-repressor complex to DNA damage

GSE1 links the HDAC1/CoREST co-repressor complex to DNA damage

Epigenetic regulation of B cells and its role in autoimmune pathogenesis

The emerging role of histone deacetylase 1 in allergic diseases

Contact Info

Product

Resources

About

Entinostat, a histone deacetylase inhibitor, increases the population of IL-10⁺regulatory B cells to suppress contact hypersensitivity