The Role of Macrophages in the Response to TNF Inhibition in Experimental Arthritis.
The Role of Macrophages in the Response to TNF Inhibition in Experimental Arthritis.
复制标题
DOI：
10.4049/jimmunol.1700229
复制
发表时间：
2018-01-01
期刊：
影响因子：
--
通讯作者：
Pope RM
中科院分区：
文献类型：
--
作者：
Huang QQ;Birkett R;Doyle R;Shi B;Roberts EL;Mao Q;Pope RM
滑膜组织巨噬细胞的减少是类风湿性关节炎（RA）患者临床改善的可靠生物标志物，并且在开始使用TNF抑制剂后不久，滑膜组织中的巨噬细胞减少。这种最初反应的机制尚不清楚。进行这些研究以确定TNF抑制后巨噬细胞初始减少的机制，假定涉及流出至引流淋巴结（LN）。RA滑膜组织和滑液巨噬细胞表达CCR 7，与TNFα孵育后，对照巨噬细胞中的CCR 7增加。人TNF转基因（hTNF-Tg）小鼠在发生关节炎后接受英夫利西单抗治疗。收集踝关节并通过组织学、免疫组织化学、qRT-PCR、ELISA和流式细胞术进行检查。用英夫利西单抗治疗的hTNF-Tg小鼠在治疗开始后3天表现出显著的临床和组织学改善，此时踝关节中的Ly 6C+巨噬细胞显著减少。然而，没有证据支持巨噬细胞流出液在英夫利西单抗治疗后对淋巴结引流的作用。相比之下，在开始英夫利西单抗治疗后，发现踝关节和腘淋巴结中Ly 6C+巨噬细胞凋亡，单核细胞向踝关节迁移减少，CCL 2减少。这些观察结果表明Ly 6C+巨噬细胞凋亡和循环单核细胞进入关节的减少是hTNF-Tg小鼠中英夫利西单抗治疗后巨噬细胞最初减少的原因。
The reduction of synovial tissue macrophage is a reliable biomarker for clinical improvement in patients with rheumatoid arthritis (RA) and macrophages are reduced in synovial tissue shortly after initiation of TNF inhibitors. The mechanism for this initial response is unclear. These studies were performed to identify the mechanisms responsible for the initial reduction of macrophages following TNF inhibition, positing that efflux to draining lymph nodes (LNs) was involved. RA synovial tissue and synovial fluid macrophages expressed CCR7, which was increased in control macrophages following incubation with TNFα. Human TNF transgenic (hTNF-Tg) mice were treated with infliximab after development of arthritis. Ankles were harvested and examined by histology, immunohistochemistry, qRT-PCR, ELISA, and flow cytometry. hTNF-Tg mice treated with infliximab demonstrated significant clinical and histologic improvement 3 days after the initiation of therapy, at which time Ly6C+ macrophages were significantly reduced in the ankles. However, no evidence was identified to support a role of macrophage efflux to draining LNs following treatment with infliximab. In contrast, apoptosis of Ly6C+ macrophages in the ankles and popliteal LNs, decreased migration of monocytes into the ankles, and a reduction of CCL2, were identified following the initiation of infliximab. These observations demonstrate that Ly6C+ macrophages apoptosis and decreased ingress of circulating monocytes into the joint are responsible for the initial reduction of macrophages following infliximab treatment in hTNF-Tg mice.
登录
查看更多内容
影响因子：
--
作者：
Scatizzi, John C.;Bickel, Emily;Perlman, Harris
通讯作者：
Perlman, Harris
影响因子：
20.3
作者：
Gautier, Emmanuel L.;Ivanov, Stoyan;Randolph, Gwendalyn J.
通讯作者：
Randolph, Gwendalyn J.
影响因子：
8.8
作者：
Russo, Erica;Teijeira, Alvaro;Halin, Cornelia
通讯作者：
Halin, Cornelia
影响因子：
27.4
作者：
Herenius, M. M. J.;Thurlings, R. M.;Tak, P. P.
通讯作者：
Tak, P. P.
影响因子：
13.3
作者：
Huang, Qi-Quan;Birkett, Robert;Pope, Richard M.
通讯作者：
Pope, Richard M.