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您的检索式：作者名="Aimee Chevalier"
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| 1 | Macrophages are the primary effector cells in IL-7-induced arthritis显示文摘Synovial macrophages are crucial in the development of joint inflammation and bone damage;however, the pathways that controlmacrophage remodeling in inflammatory M1 cells or bone-eroding osteoclasts are not fully understood. We determined thatelevated IL-7R/CD127 expression is the hallmark of rheumatoid arthritis (RA) M1 macrophages and that these cells are highlyresponsive to interleukin-7 (IL-7)-driven osteoclastogenesis. We established that lipopolysaccharide (LPS), interferon-γ (IFNγ), andtumor necrosis factor-α (TNFα), the classic M1 macrophage mediators, enhance IL-7R expression in RA and murine macrophages.The local expression of IL-7 provokes arthritis, predominantly through escalating the number of F480^(+)iNOS^(+) cells rather than CD3^(+)T cells. Ectopic LPS injection stabilizes IL-7-induced arthritis by increasing myeloid IL-7R expression, in part via IFNγ induction.Hence, in RAG−/− mice, IL-7-mediated arthritis is suppressed because of the reduction in myeloid IL-7R expression due to the lackof IFNγ. Moreover, the amelioration of IL-7-induced arthritis by anti-TNF therapy is due to a decrease in the number of cells in theunique F480^(+)iNOS^(+)IL-7R^(+)CCL5^(+) subset, with no impact on the F480^(+)Arginase^(+) cell or CD3^(+) T cell frequency. Consistent with thepreclinical findings, the findings of a phase 4 study performed with RA patients following 6 months of anti-TNF therapy revealedthat IL-7R expression was reduced without affecting the levels of IL-7. This study shifts the paradigm by discovering that IL-7-induced arthritis is dependent on F480^(+)iNOS^(+)IL-7R^(+)CCL5^(+) cell function, which activates TH-1 cells to amplify myeloid IL-7Rexpression and disease severity. | Seung-jae Kim Huan J.Chang Michael VVolin Sadiq Umar Katrien Van Raemdonck Aimee Chevalier Karol Palasiewicz John W.Christman Suncica Volkov Shiva Arami Mehrdad Maz Anjali Mehta Ryan K.Zomorrodi David A.Fox Nadera Sweiss Shiva Shahrara | 2020 | Cellular & Molecular Immunology2020，17，7： | 4 |
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