CD23+/CD21hi B-cell translocation and ipsilateral lymph node collapse is associated with asymmetric arthritic flare in TNF-Tg mice
CD23+/CD21hi B-cell translocation and ipsilateral lymph node collapse is associated with asymmetric arthritic flare in TNF-Tg mice
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DOI：
10.1186/ar3452
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发表时间：
2011-01-01
影响因子：
4.9
通讯作者：
Schwarz, Edward M.
中科院分区：
文献类型：
--
作者：
Li, Jie;Zhou, Quan;Schwarz, Edward M.
前言：类风湿性关节炎(RA)是一种慢性自身免疫性疾病，在受累关节出现阵发性红斑。然而，在全身性自身免疫性疾病期间，关节炎发作如何只发生在选定的关节仍然是一个谜。为了更好地理解这些观察结果，我们在RA小鼠模型中发展了滑膜炎和淋巴流的纵向成像结果，并发现不对称膝关节肿胀与同侧延髓淋巴结(PLN)塌陷和CD23(+)/CD21(Hi)B细胞(B-in)移位到结节的皮质旁窦间隙有关。为了了解这种B-in易位与肿胀关节淋巴引流的关系，我们验证了不对称肿瘤坏死因子(TNF)诱导的膝关节炎与同侧PLN和髂骨淋巴结(ILN)塌陷、B-in易位以及传入淋巴流量减少有关的假说。方法：通过对比增强(CE)磁共振成像(MRI)对非对称性膝关节炎的肿瘤坏死因子转基因(TG)小鼠进行鉴定，并使用LNCaP Threshold=30(任意单位(AU))将PLN分型为“扩张”或“塌陷”。炎性侵袭性关节炎经组织学证实。通过注射吲哚青绿的近红外成像(NIR-ICG)对PLN和ILN的传入淋巴流量进行定量。免疫组织化学(IHC)和流式细胞术检测PLN和ILN中的B细胞亚群。结果：NIR-ICG图像显示，流向塌陷结节的传入淋巴流量显著低于流向扩张结节的传入淋巴流量(P<；0.05)，且均发生在同侧。萎缩型和扩张型PLN和ILN的B-in含量均显著高于野生型(WT)和炎性前肿瘤坏死因子-TG结节(P<；0.05)，扩张淋巴结(LN)的B-in位于滤泡区，而塌陷型LN的B-in存在于Lyve-1+淋巴管内。在膝关节滑膜炎期间，同侧PLN和ILN之间的传入淋巴流量存在显著的相关性(P<；0.002)。结论：肿瘤坏死因子-TG小鼠的不对称膝关节炎与同侧PLN和ILN的塌陷同时发生。这可能是由于扩大的B-in人群移位到淋巴管腔，导致传入淋巴流量显著减少。PLN塌陷表型可作为膝关节红肿的一个新的生物标志物。
Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease with episodic flares in affected joints. However, how arthritic flare occurs only in select joints during a systemic autoimmune disease remains an enigma. To better understand these observations, we developed longitudinal imaging outcomes of synovitis and lymphatic flow in mouse models of RA, and identified that asymmetric knee flare is associated with ipsilateral popliteal lymph node (PLN) collapse and the translocation of CD23(+)/CD21(hi) B-cells (B-in) into the paracortical sinus space of the node. In order to understand the relationship between this B-in translocation and lymph drainage from flaring joints, we tested the hypothesis that asymmetric tumor necrosis factor (TNF)-induced knee arthritis is associated with ipsilateral PLN and iliac lymph node (ILN) collapse, B-in translocation, and decreased afferent lymphatic flow.Methods: TNF transgenic (Tg) mice with asymmetric knee arthritis were identified by contrast-enhanced (CE) magnetic resonance imaging (MRI), and PLN were phenotyped as "expanding" or "collapsed" using LNcap threshold = 30 (Arbitrary Unit (AU)). Inflammatory-erosive arthritis was confirmed by histology. Afferent lymphatic flow to PLN and ILN was quantified by near infrared imaging of injected indocyanine green (NIR-ICG). The B-in population in PLN and ILN was assessed by immunohistochemistry (IHC) and flow cytometry. Linear regression analyses of ipsilateral knee synovial volume and afferent lymphatic flow to PLN and ILN were performed.Results: Afferent lymph flow to collapsed nodes was significantly lower (P < 0.05) than flow to expanding nodes by NIR-ICG imaging, and this occurred ipsilaterally. While both collapsed and expanding PLN and ILN had a significant increase (P < 0.05) of B-in compared to wild type (WT) and pre-arthritic TNF-Tg nodes, B-in of expanding lymph nodes (LN) resided in follicular areas while B-in of collapsed LN were present within LYVE-1+ lymphatic vessels. A significant correlation (P < 0.002) was noted in afferent lymphatic flow between ipsilateral PLN and ILN during knee synovitis.Conclusions: Asymmetric knee arthritis in TNF-Tg mice occurs simultaneously with ipsilateral PLN and ILN collapse. This is likely due to translocation of the expanded B-in population to the lumen of the lymphatic vessels, resulting in a dramatic decrease in afferent lymphatic flow. PLN collapse phenotype can serve as a new biomarker of knee flare.