AUTHOR=Bekaddour Nassima , Smith Nikaïa , Beitz Benoit , Llibre Alba , Dott Tom , Baudry Anne , Korganow Anne-Sophie , Nisole Sébastien , Mouy Richard , Breton Sylvain , Bader-Meunier Brigitte , Duffy Darragh , Terrier Benjamin , Schneider Benoit , Quartier Pierre , Rodero Mathieu P. , Herbeuval Jean-Philippe TITLE=Targeting the chemokine receptor CXCR4 with histamine analog to reduce inflammation in juvenile arthritis JOURNAL=Frontiers in Immunology VOLUME=Volume 14 - 2023 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1178172 DOI=10.3389/fimmu.2023.1178172 ISSN=1664-3224 ABSTRACT=Among immune cells, activated monocytes play a detrimental role in chronic and viral-induced inflammatory pathologies. The uncontrolled activation of monocytes and the subsequent excessive production of inflammatory factors damage bone-cartilage joints in Juvenile Idiopathic Arthritis (JIA), a childhood rheumatoid arthritis (RA) disease. The moderate beneficial effect of current therapies and clinical trials highlights the need of alternative strategies targeting monocytes to treat RA disease. Here, we show that targeting CXCR4 with small amino compound such as the histamine analog clobenpropit (CB) inhibits spontaneous and induced-production of a set of key inflammatory cytokines by monocytes isolated from blood and synovial fluids of JIA patients. Moreover, daily intraperitoneal CB treatment of arthritic mice results in significant decrease in circulating inflammatory cytokine levels, immune cell infiltrates, joints erosion, and bone resorption leading to reduction of disease progression. These overall data show that targeting CXCR4 with CB-like molecules may represent a promising therapeutic option for chronic and viral-induced inflammatory diseases.