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Dalloul Z, Best M, Chenuet P, et al. Bromodomain and extraterminal (BET) protein inhibition of IgG/IgE production in murine B cells is counter-balanced by a strong Th2 bias. Clin Transl Immunology. 2021;10(6):e1280doi: 10.1002/cti2.1280.
Dalloul, Z., Best, M., Chenuet, P., Dalloul, I., Le Noir, S., Togbé, D., Gador, M., Ryffel, B., Fj Quesniaux, V., El Makhour, Y., Boyer, F., Aldigier, J. C., Cook-Moreau, J., Fazilleau, N., & Cogné, M. (2021). Bromodomain and extraterminal (BET) protein inhibition of IgG/IgE production in murine B cells is counter-balanced by a strong Th2 bias. Clinical & translational immunology, 10(6), e1280. https://doi.org/10.1002/cti2.1280
Dalloul, Zeinab, et al. "Bromodomain and extraterminal (BET) protein inhibition of IgG/IgE production in murine B cells is counter-balanced by a strong Th2 bias." Clinical & translational immunology vol. 10,6 (2021): e1280. doi: https://doi.org/10.1002/cti2.1280
Dalloul Z, Best M, Chenuet P, Dalloul I, Le Noir S, Togbé D, Gador M, Ryffel B, Fj Quesniaux V, El Makhour Y, Boyer F, Aldigier JC, Cook-Moreau J, Fazilleau N, Cogné M. Bromodomain and extraterminal (BET) protein inhibition of IgG/IgE production in murine B cells is counter-balanced by a strong Th2 bias. Clin Transl Immunology. 2021 May 30;10(6):e1280. doi: 10.1002/cti2.1280. eCollection 2021. PMID: 34136216; PMCID: PMC8164936.
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Clin Transl Immunology. 2021 May 30;10(6):e1280. doi: 10.1002/cti2.1280. eCollection 2021.

Bromodomain and extraterminal (BET) protein inhibition of IgG/IgE production in murine B cells is counter-balanced by a strong Th2 bias.

Clinical & translational immunology

Zeinab Dalloul, Marie Best, Pauline Chenuet, Iman Dalloul, Sandrine Le Noir, Dieudonnée Togbé, Mylène Gador, Bernhard Ryffel, Valerie Fj Quesniaux, Yolla El Makhour, François Boyer, Jean-Claude Aldigier, Jeanne Cook-Moreau, Nicolas Fazilleau, Michel Cogné

Affiliations

  1. Control of the B cell Response & Lymphoproliferation CNRS UMR 7276 INSERM U1262 Limoges University Limoges France.
  2. Infinity-Toulouse Institute for Infectious and Inflammatory Diseases CNRS U5051, Inserm U1291 University of Toulouse III Toulouse France.
  3. INEM - UMR7355 CNRS Orléans France.
  4. ArtImmune SAS Orléans France.
  5. Faculty of Sciences Immunology Unit MICSU and Lebanese University Beirut Lebanon.
  6. INSERM U 1236 University of Rennes 1 Rennes France.

PMID: 34136216 PMCID: PMC8164936 DOI: 10.1002/cti2.1280

Abstract

OBJECTIVES: Inhibitors of bromodomain and extra terminal domain (BET) proteins are a new and growing class of anti-cancer drugs, which decrease oncogene expression by targeting superenhancers. Antibody production is another physiological process relying on superenhancers, and it remains to be clarified whether potential immunomodulatory properties of BET inhibitors might impact humoral immunity and allergy.

METHODS: We thus evaluated humoral immune responses and their Th2 context

RESULTS: Bromodomain and extra terminal domain inhibition reduced class switching, Ig expression on B cells and antibody secretion and was correlated with decreased numbers of Tfh cells. However, JQ1 strongly increased the proportion of GATA3

CONCLUSION: Altogether, BET inhibition thus interweaves intrinsic negative effects on B cells with a parallel complex reshaping of T-cell polarisation which can increase type 2 cytokines and eventually promote B-cell-dependent immunopathology. These opposite and potentially hazardous immunomodulatory effects raise concerns for clinical use of BET inhibitors in patients with immune disorders.

© 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.

Keywords: allergic inflammation; antibody class switching; bromodomain inhibition; immune response

Conflict of interest statement

D Togbe and P Chenuet are employees at ArtImmune. All the authors have no conflict of interest related to this study.

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