Targeting the chemokine receptor CXCR4 with histamine analog to reduce inflammation in juvenile arthritis
IntroductionAmong immune cells, activated monocytes play a detrimental role in chronic and viral-induced inflammatory pathologies, particularly in Juvenile Idiopathic Arthritis (JIA), a childhood rheumatoid arthritis (RA) disease. The uncontrolled activation of monocytes and excessive production of...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1178172/full |
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| author | Nassima Bekaddour Nassima Bekaddour Nikaïa Smith Benoit Beitz Alba Llibre Tom Dott Anne Baudry Anne-Sophie Korganow Anne-Sophie Korganow Anne-Sophie Korganow Sébastien Nisole Richard Mouy Sylvain Breton Sylvain Breton Brigitte Bader-Meunier Brigitte Bader-Meunier Darragh Duffy Benjamin Terrier Benoit Schneider Pierre Quartier Pierre Quartier Mathieu P. Rodero Mathieu P. Rodero Jean-Philippe Herbeuval Jean-Philippe Herbeuval |
| author_facet | Nassima Bekaddour Nassima Bekaddour Nikaïa Smith Benoit Beitz Alba Llibre Tom Dott Anne Baudry Anne-Sophie Korganow Anne-Sophie Korganow Anne-Sophie Korganow Sébastien Nisole Richard Mouy Sylvain Breton Sylvain Breton Brigitte Bader-Meunier Brigitte Bader-Meunier Darragh Duffy Benjamin Terrier Benoit Schneider Pierre Quartier Pierre Quartier Mathieu P. Rodero Mathieu P. Rodero Jean-Philippe Herbeuval Jean-Philippe Herbeuval |
| author_sort | Nassima Bekaddour |
| collection | DOAJ |
| description | IntroductionAmong immune cells, activated monocytes play a detrimental role in chronic and viral-induced inflammatory pathologies, particularly in Juvenile Idiopathic Arthritis (JIA), a childhood rheumatoid arthritis (RA) disease. The uncontrolled activation of monocytes and excessive production of inflammatory factors contribute to the damage of bone-cartilage joints. Despite the moderate beneficial effect of current therapies and clinical trials, there is still a need for alternative strategies targeting monocytes to treat RA.MethodsTo explore such an alternative strategy, we investigated the effects of targeting the CXCR4 receptor using the histamine analog clobenpropit (CB). Monocytes were isolated from the blood and synovial fluids of JIA patients to assess CB's impact on their production of key inflammatory cytokines. Additionally, we administered daily intraperitoneal CB treatment to arthritic mice to evaluate its effects on circulating inflammatory cytokine levels, immune cell infiltrates, joints erosion, and bone resorption, as indicators of disease progression.ResultsOur findings demonstrated that CXCR4 targeting with CB significantly inhibited the spontaneous and induced-production of key inflammatory cytokines by monocytes isolated from JIA patients. Furthermore, CB treatment in a mouse model of collagen-induce arthritis resulted in a significant decrease in circulating inflammatory cytokine levels, immune cell infiltrates, joints erosion, and bone resorption, leading to a reduction in disease progression.DiscussionIn conclusion, targeting CXCR4 with the small amino compound CB shows promise as a therapeutic option for chronic and viral-induced inflammatory diseases, including RA. CB effectively regulated inflammatory cytokine production of monocytes, presenting a potential targeted approach with potential advantages over current therapies. These results warrant further research and clinical trials to explore the full therapeutic potential of targeting CXCR4 with CB-like molecules in the management of various inflammatory diseases. |
| first_indexed | 2024-03-11T21:29:36Z |
| format | Article |
| id | doaj.art-211367eb2e744db5b42f0c81bd117414 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T21:29:36Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-211367eb2e744db5b42f0c81bd1174142023-09-27T10:24:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.11781721178172Targeting the chemokine receptor CXCR4 with histamine analog to reduce inflammation in juvenile arthritisNassima Bekaddour0Nassima Bekaddour1Nikaïa Smith2Benoit Beitz3Alba Llibre4Tom Dott5Anne Baudry6Anne-Sophie Korganow7Anne-Sophie Korganow8Anne-Sophie Korganow9Sébastien Nisole10Richard Mouy11Sylvain Breton12Sylvain Breton13Brigitte Bader-Meunier14Brigitte Bader-Meunier15Darragh Duffy16Benjamin Terrier17Benoit Schneider18Pierre Quartier19Pierre Quartier20Mathieu P. Rodero21Mathieu P. Rodero22Jean-Philippe Herbeuval23Jean-Philippe Herbeuval24Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR)-8601, Université Paris Cité, Paris, FranceChemistry and Biology, Modeling and Immunology for Therapy (CBMIT), Paris, FranceTranslational Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, FranceBIOASTER, Lyon, FranceTranslational Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, FranceBIOASTER, Lyon, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR)-S1124, Team Stem Cells, Signaling and Prions, Université Paris Cité, Paris, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) - S1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, FranceDepartment of Clinical Immunology and Internal Medicine, National Reference Center for Rare Autoimmune Diseases Centre National de Référence des maladies auto-immunes et systémiques rares de Strasbourg (RESO), Hôpitaux Universitaires de Strasbourg, Strasbourg, FranceUnité de Formation et de Recherche (UFR) Medicine, University of Strasbourg, Strasbourg, FranceInstitut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 9004, Montpellier, France0Paediatric Haematology-Immunology and Rheumatology Department, Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l'enfant (RAISE) Reference Centre for Rare Diseases, Hôpital Universitaire Necker, Assistance Publique-Hôpitaux de Paris, Paris, France0Paediatric Haematology-Immunology and Rheumatology Department, Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l'enfant (RAISE) Reference Centre for Rare Diseases, Hôpital Universitaire Necker, Assistance Publique-Hôpitaux de Paris, Paris, France1Paediatric Radiology Department, Necker-Enfants Malades University Hospital, Paris, France0Paediatric Haematology-Immunology and Rheumatology Department, Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l'enfant (RAISE) Reference Centre for Rare Diseases, Hôpital Universitaire Necker, Assistance Publique-Hôpitaux de Paris, Paris, France2Pediatric Immunology-Hematology and Rheumatology Unit, Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM U1163, Necker-Enfants Malades Hospital, Assistance Publique - Hôpitaux de Paris (APHP), Imagine Institute, Université Paris Cité, Paris, FranceTranslational Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, France3Department of Internal Medicine, National Referral Center for Rare Systemic Autoimmune Diseases, Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Université de Paris, Paris, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR)-S1124, Team Stem Cells, Signaling and Prions, Université Paris Cité, Paris, France0Paediatric Haematology-Immunology and Rheumatology Department, Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l'enfant (RAISE) Reference Centre for Rare Diseases, Hôpital Universitaire Necker, Assistance Publique-Hôpitaux de Paris, Paris, France2Pediatric Immunology-Hematology and Rheumatology Unit, Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM U1163, Necker-Enfants Malades Hospital, Assistance Publique - Hôpitaux de Paris (APHP), Imagine Institute, Université Paris Cité, Paris, FranceCentre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR)-8601, Université Paris Cité, Paris, FranceChemistry and Biology, Modeling and Immunology for Therapy (CBMIT), Paris, FranceCentre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR)-8601, Université Paris Cité, Paris, FranceChemistry and Biology, Modeling and Immunology for Therapy (CBMIT), Paris, FranceIntroductionAmong immune cells, activated monocytes play a detrimental role in chronic and viral-induced inflammatory pathologies, particularly in Juvenile Idiopathic Arthritis (JIA), a childhood rheumatoid arthritis (RA) disease. The uncontrolled activation of monocytes and excessive production of inflammatory factors contribute to the damage of bone-cartilage joints. Despite the moderate beneficial effect of current therapies and clinical trials, there is still a need for alternative strategies targeting monocytes to treat RA.MethodsTo explore such an alternative strategy, we investigated the effects of targeting the CXCR4 receptor using the histamine analog clobenpropit (CB). Monocytes were isolated from the blood and synovial fluids of JIA patients to assess CB's impact on their production of key inflammatory cytokines. Additionally, we administered daily intraperitoneal CB treatment to arthritic mice to evaluate its effects on circulating inflammatory cytokine levels, immune cell infiltrates, joints erosion, and bone resorption, as indicators of disease progression.ResultsOur findings demonstrated that CXCR4 targeting with CB significantly inhibited the spontaneous and induced-production of key inflammatory cytokines by monocytes isolated from JIA patients. Furthermore, CB treatment in a mouse model of collagen-induce arthritis resulted in a significant decrease in circulating inflammatory cytokine levels, immune cell infiltrates, joints erosion, and bone resorption, leading to a reduction in disease progression.DiscussionIn conclusion, targeting CXCR4 with the small amino compound CB shows promise as a therapeutic option for chronic and viral-induced inflammatory diseases, including RA. CB effectively regulated inflammatory cytokine production of monocytes, presenting a potential targeted approach with potential advantages over current therapies. These results warrant further research and clinical trials to explore the full therapeutic potential of targeting CXCR4 with CB-like molecules in the management of various inflammatory diseases.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1178172/fullmonocytescytokinesarthritisinflammationtreatment |
| spellingShingle | Nassima Bekaddour Nassima Bekaddour Nikaïa Smith Benoit Beitz Alba Llibre Tom Dott Anne Baudry Anne-Sophie Korganow Anne-Sophie Korganow Anne-Sophie Korganow Sébastien Nisole Richard Mouy Sylvain Breton Sylvain Breton Brigitte Bader-Meunier Brigitte Bader-Meunier Darragh Duffy Benjamin Terrier Benoit Schneider Pierre Quartier Pierre Quartier Mathieu P. Rodero Mathieu P. Rodero Jean-Philippe Herbeuval Jean-Philippe Herbeuval Targeting the chemokine receptor CXCR4 with histamine analog to reduce inflammation in juvenile arthritis Frontiers in Immunology monocytes cytokines arthritis inflammation treatment |
| title | Targeting the chemokine receptor CXCR4 with histamine analog to reduce inflammation in juvenile arthritis |
| title_full | Targeting the chemokine receptor CXCR4 with histamine analog to reduce inflammation in juvenile arthritis |
| title_fullStr | Targeting the chemokine receptor CXCR4 with histamine analog to reduce inflammation in juvenile arthritis |
| title_full_unstemmed | Targeting the chemokine receptor CXCR4 with histamine analog to reduce inflammation in juvenile arthritis |
| title_short | Targeting the chemokine receptor CXCR4 with histamine analog to reduce inflammation in juvenile arthritis |
| title_sort | targeting the chemokine receptor cxcr4 with histamine analog to reduce inflammation in juvenile arthritis |
| topic | monocytes cytokines arthritis inflammation treatment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1178172/full |
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