The histamine analogue clobenpropit modulates IRF7 phosphorylation and interferon production by targeting CXCR4 in systemic lupus erythematosus models
IntroductionSystemic 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. Cur...
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Frontiers Media S.A.
2024-12-01
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| author | Nassima Bekaddour Nassima Bekaddour Nikaïa Smith Birgit Caspar Birgit Caspar Severine Grinberg Severine Grinberg Stephane Giorgiutti Stephane Giorgiutti Stephane Giorgiutti Vincent Rodeschini Stephanie Dupuy Nicolas Leboulanger Nicolas Leboulanger Darragh Duffy Pauline Soulas-Sprauel Pauline Soulas-Sprauel Pauline Soulas-Sprauel Vincent Gies Vincent Gies Vincent Gies Anne-Sophie Korganow Anne-Sophie Korganow Anne-Sophie Korganow Sébastien Nisole Jean-Philippe Herbeuval Jean-Philippe Herbeuval |
| author_facet | Nassima Bekaddour Nassima Bekaddour Nikaïa Smith Birgit Caspar Birgit Caspar Severine Grinberg Severine Grinberg Stephane Giorgiutti Stephane Giorgiutti Stephane Giorgiutti Vincent Rodeschini Stephanie Dupuy Nicolas Leboulanger Nicolas Leboulanger Darragh Duffy Pauline Soulas-Sprauel Pauline Soulas-Sprauel Pauline Soulas-Sprauel Vincent Gies Vincent Gies Vincent Gies Anne-Sophie Korganow Anne-Sophie Korganow Anne-Sophie Korganow Sébastien Nisole Jean-Philippe Herbeuval Jean-Philippe Herbeuval |
| author_sort | Nassima Bekaddour |
| collection | DOAJ |
| description | IntroductionSystemic 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.MethodsOur study introduces clobenpropit, a histamine analogue, as a potential new therapy targeting the CXCR4 receptor to reduce IRF7 phosphorylation and subsequent interferon production. We employed various laboratory techniques to investigate how clobenpropit interacts with CXCR4 and its effects on immune cells from healthy individuals and SLE patients.ResultsClobenpropit binds effectively to CXCR4, significantly inhibiting IRF7 phosphorylation and reducing interferon production. Additionally, clobenpropit lowered levels of pro-inflammatory cytokines in a mouse model of lupus, demonstrating efficacy comparable to the standard treatment, prednisolone.DiscussionThese results suggest that clobenpropit could be a promising new treatment for SLE, offering a targeted approach with potential advantages over current therapies. |
| format | Article |
| id | doaj-art-a09c3482328d4c76aaf5b31c9b67450d |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-a09c3482328d4c76aaf5b31c9b67450d2024-12-16T05:10:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.14905931490593The histamine analogue clobenpropit modulates IRF7 phosphorylation and interferon production by targeting CXCR4 in systemic lupus erythematosus modelsNassima Bekaddour0Nassima Bekaddour1Nikaïa Smith2Birgit Caspar3Birgit Caspar4Severine Grinberg5Severine Grinberg6Stephane Giorgiutti7Stephane Giorgiutti8Stephane Giorgiutti9Vincent Rodeschini10Stephanie Dupuy11Nicolas Leboulanger12Nicolas Leboulanger13Darragh Duffy14Pauline Soulas-Sprauel15Pauline Soulas-Sprauel16Pauline Soulas-Sprauel17Vincent Gies18Vincent Gies19Vincent Gies20Anne-Sophie Korganow21Anne-Sophie Korganow22Anne-Sophie Korganow23Sébastien Nisole24Jean-Philippe Herbeuval25Jean-Philippe Herbeuval26Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR), Université Paris Cité, Paris, FranceTeam Chemistry & Biology, Modeling & Immunology for Therapy (CBMIT), Paris, FranceTranslational Immunology Unit, Institut Pasteur, Université Paris-Cité, Paris, FranceCentre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR), Université Paris Cité, Paris, FranceTeam Chemistry & Biology, Modeling & Immunology for Therapy (CBMIT), Paris, FranceCentre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR), Université Paris Cité, Paris, FranceTeam Chemistry & Biology, Modeling & Immunology for Therapy (CBMIT), Paris, FranceUniversité de Strasbourg, Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) S1109, Institut Thématique Interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Transplantation Excellence Nouvelle Génération (Transplantex NG), Fédération Hospitalo-Universitaire OMICs for Care (OMICARE), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, FranceDepartment of Clinical Immunology and Internal Medicine, National Reference Center for Systemic Autoimmune Diseases (Centre de Référence des Maladies Auto-Immunes Rares de Strasbourg, (CNR RESO)), Tertiary Center for Primary Immunodeficiency, Strasbourg University Hospital, Strasbourg, FranceUniversité de Strasbourg, Faculty of Medicine, Strasbourg, FranceEdelris, Lyon, FranceUnité d’Appui et de Recherche (UAR) BioMedTech Facilities, Plateforme cyto2Bm, Université Paris Cité, Paris, FranceFaculté de Médecine, Université Paris Cité, Paris, France0Department of Paediatric Otolaryngology, Assistance Publique – Hôpitaux de Paris (AP-HP), Hôpital Necker-Enfants Malades, Paris, FranceTranslational Immunology Unit, Institut Pasteur, Université Paris-Cité, Paris, FranceUniversité de Strasbourg, Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) S1109, Institut Thématique Interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Transplantation Excellence Nouvelle Génération (Transplantex NG), Fédération Hospitalo-Universitaire OMICs for Care (OMICARE), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, FranceDepartment of Clinical Immunology and Internal Medicine, National Reference Center for Systemic Autoimmune Diseases (Centre de Référence des Maladies Auto-Immunes Rares de Strasbourg, (CNR RESO)), Tertiary Center for Primary Immunodeficiency, Strasbourg University Hospital, Strasbourg, FranceUniversité de Strasbourg, Faculty of Medicine, Strasbourg, FranceUniversité de Strasbourg, Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) S1109, Institut Thématique Interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Transplantation Excellence Nouvelle Génération (Transplantex NG), Fédération Hospitalo-Universitaire OMICs for Care (OMICARE), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, FranceDepartment of Clinical Immunology and Internal Medicine, National Reference Center for Systemic Autoimmune Diseases (Centre de Référence des Maladies Auto-Immunes Rares de Strasbourg, (CNR RESO)), Tertiary Center for Primary Immunodeficiency, Strasbourg University Hospital, Strasbourg, France1Université de Strasbourg, Faculty of Pharmacy, Strasbourg, FranceUniversité de Strasbourg, Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) S1109, Institut Thématique Interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Transplantation Excellence Nouvelle Génération (Transplantex NG), Fédération Hospitalo-Universitaire OMICs for Care (OMICARE), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, FranceDepartment of Clinical Immunology and Internal Medicine, National Reference Center for Systemic Autoimmune Diseases (Centre de Référence des Maladies Auto-Immunes Rares de Strasbourg, (CNR RESO)), Tertiary Center for Primary Immunodeficiency, Strasbourg University Hospital, Strasbourg, FranceUniversité de Strasbourg, Faculty of Medicine, Strasbourg, France2Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 9004, Montpellier, FranceCentre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR), Université Paris Cité, Paris, FranceTeam Chemistry & Biology, Modeling & Immunology for Therapy (CBMIT), Paris, FranceIntroductionSystemic 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.MethodsOur study introduces clobenpropit, a histamine analogue, as a potential new therapy targeting the CXCR4 receptor to reduce IRF7 phosphorylation and subsequent interferon production. We employed various laboratory techniques to investigate how clobenpropit interacts with CXCR4 and its effects on immune cells from healthy individuals and SLE patients.ResultsClobenpropit binds effectively to CXCR4, significantly inhibiting IRF7 phosphorylation and reducing interferon production. Additionally, clobenpropit lowered levels of pro-inflammatory cytokines in a mouse model of lupus, demonstrating efficacy comparable to the standard treatment, prednisolone.DiscussionThese results suggest that clobenpropit could be a promising new treatment for SLE, offering a targeted approach with potential advantages over current therapies.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1490593/fullinterferonspDcSLECXCR4pIRF7 |
| spellingShingle | Nassima Bekaddour Nassima Bekaddour Nikaïa Smith Birgit Caspar Birgit Caspar Severine Grinberg Severine Grinberg Stephane Giorgiutti Stephane Giorgiutti Stephane Giorgiutti Vincent Rodeschini Stephanie Dupuy Nicolas Leboulanger Nicolas Leboulanger Darragh Duffy Pauline Soulas-Sprauel Pauline Soulas-Sprauel Pauline Soulas-Sprauel Vincent Gies Vincent Gies Vincent Gies Anne-Sophie Korganow Anne-Sophie Korganow Anne-Sophie Korganow Sébastien Nisole Jean-Philippe Herbeuval Jean-Philippe Herbeuval The histamine analogue clobenpropit modulates IRF7 phosphorylation and interferon production by targeting CXCR4 in systemic lupus erythematosus models Frontiers in Immunology interferons pDc SLE CXCR4 pIRF7 |
| title | The histamine analogue clobenpropit modulates IRF7 phosphorylation and interferon production by targeting CXCR4 in systemic lupus erythematosus models |
| title_full | The histamine analogue clobenpropit modulates IRF7 phosphorylation and interferon production by targeting CXCR4 in systemic lupus erythematosus models |
| title_fullStr | The histamine analogue clobenpropit modulates IRF7 phosphorylation and interferon production by targeting CXCR4 in systemic lupus erythematosus models |
| title_full_unstemmed | The histamine analogue clobenpropit modulates IRF7 phosphorylation and interferon production by targeting CXCR4 in systemic lupus erythematosus models |
| title_short | The histamine analogue clobenpropit modulates IRF7 phosphorylation and interferon production by targeting CXCR4 in systemic lupus erythematosus models |
| title_sort | histamine analogue clobenpropit modulates irf7 phosphorylation and interferon production by targeting cxcr4 in systemic lupus erythematosus models |
| topic | interferons pDc SLE CXCR4 pIRF7 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1490593/full |
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