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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1490593

The Histamine Analogue Clobenpropit Modulates IRF7 Phosphorylation and Interferon Production by targeting CXCR4 in Systemic Lupus Erythematosus models

Provisionally accepted
Nassima Bekaddour Nassima Bekaddour 1,2*Nikaïa Smith Nikaïa Smith 3Birgit Caspar Birgit Caspar 1,2Severine Grinberg Severine Grinberg 1,2Stephane Giorgiutti Stephane Giorgiutti 4Vincent Rodeschini Vincent Rodeschini 5Stephanie Dupuy Stephanie Dupuy 1Nicolas Leboulanger Nicolas Leboulanger 1Darragh Duffy Darragh Duffy 3Pauline Soulas-Sprauel Pauline Soulas-Sprauel 4Vincent Gies Vincent Gies 4Anne-Sophie Korganow Anne-Sophie Korganow 4Sébastien Nisole Sébastien Nisole 6Jean-philippe Herbeuval Jean-philippe Herbeuval 1,2
  • 1 Université Paris Cité, Paris, France
  • 2 UMR8601 Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Paris, Île-de-France, France
  • 3 Institut Pasteur, Paris, Île-de-France, France
  • 4 Université de Strasbourg, Strasbourg, Alsace, France
  • 5 Edelris, Lyon, France
  • 6 UMR9004 Institut de Recherche en Infectiologie de Montpellier (IRIM), Montpellier, Languedoc-Roussillon, France

The final, formatted version of the article will be published soon.

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by an overactive immune response, particularly involving excessive production of type I interferons. This overproduction is driven by the phosphorylation of IRF7, a crucial factor in interferon gene activation. Current treatments for SLE are often not very effective and can have serious side effects. Our study introduces clobenpropit (CB), a histamine analogue, as a potential new therapy that targets the CXCR4 receptor to reduce IRF7 phosphorylation and subsequent interferon production. We used a variety of laboratory techniques to investigate how CB interacts with CXCR4 and its effects on immune cells from both healthy individuals and SLE patients. Our findings show that CB binds effectively to CXCR4, significantly inhibiting IRF7 phosphorylation and reducing CB interferon production. Additionally, CB lowered levels of pro-inflammatory cytokines in a mouse model of lupus, showing similar efficacy to the standard treatment, prednisolone. These results suggest that CB could be a promising new treatment for SLE.

    Keywords: Interferons, pDc, SLE, CXCR4, pIRF7

    Received: 03 Sep 2024; Accepted: 27 Nov 2024.

    Copyright: © 2024 Bekaddour, Smith, Caspar, Grinberg, Giorgiutti, Rodeschini, Dupuy, Leboulanger, Duffy, Soulas-Sprauel, Gies, Korganow, Nisole and Herbeuval. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Nassima Bekaddour, Université Paris Cité, Paris, France

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.