| 1 | Inflammatory macrophages exacerbate neutrophil-driven joint damage through ADP/P2Y_(1)signaling in rheumatoid arthritis显示文摘Rheumatoid arthritis(RA)is a chronic autoimmune disease that primarily affects the joints and is associated with excessive immune cell infiltration.However,the complex interactions between the immune cell populations in the RA synovium remain unknown.Here,we demonstrate that inflammatory macrophages in the synovium exacerbate neutrophil-driven joint damage in RA through ADP/P2Y_(1)signaling.We show that extracellular ADP(e ADP)and its receptors are obviously increased in synovial tissues of RA patients as well as collagen-induced arthritis(CIA)mice,and e ADP enhances neutrophil infiltration into joints through macrophages producing the chemokine CXCL2,aggravating disease development.Accordingly,the arthritis mouse model had more neutrophils in inflamed joints following ADP injection,whereas P2Y_(1)deficiency and pharmacologic inhibition restored arthritis severity to basal levels,suggesting a dominant role of ADP/P2Y_(1)signaling in RA pathology.Moreover,cellular activity of ADP/P2Y_(1)-mediated CXCL2 production was dependent on the G_(αq)/Ca^(2+)-NF-κB/NFAT pathway in macrophages.Overall,this study reveals a non-redundant role of e ADP as a trigger in the pathogenesis of RA through neutrophil recruitment and disrupted tissue homeostasis and function. | Xiaoyu Zhang Wenxiang Zhao Yihan Zhao Zeda Zhao Zhangsheng Lv Zhen Zhang Hua Ren Qin Wang Mingyao Liu Min Qian Bing Du Juliang Qin | 2022 | Science China(Life Sciences)2022，65，5： | 0 |
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