Why do leucocytes accumulate within chronically inflamed joints?
Why do leucocytes accumulate within chronically inflamed joints?
复制标题
DOI：
10.1093/rheumatology/keg413
复制
发表时间：
2003-12-01
期刊：
影响因子：
5.5
通讯作者：
Buckley, CD
中科院分区：
文献类型：
--
作者：
Buckley, CD
慢性炎症的特征是白细胞在组织内积聚。在类风湿性关节炎中，炎症浸润与淋巴组织有许多共同的结构特征。例如，CD4 T 细胞和 B 细胞积聚在滑膜组织内的血管周围淋巴结构中。 CD8 T 细胞和中性粒细胞主要存在于滑液中。驱动这些独特的淋巴微结构的因素以及淋巴细胞和成纤维细胞等基质细胞对此过程的相对贡献是本次综述的主题。白细胞和基质细胞（例如巨噬细胞和成纤维细胞）之间的细胞相互作用对于在发炎滑膜内产生肿瘤坏死因子-α非常重要。因此，了解白细胞如何在发炎的滑膜内积聚可能会提供新的治疗方法来改变炎症过程。我们发现成纤维细胞在类风湿性关节炎紊乱的滑膜微环境中起主导作用。通过产生多种细胞因子（干扰素-β、转化生长因子-β）和组成型趋化因子（基质细胞衍生因子-1、CXCL12），它们直接改变慢性炎症关节内积累的淋巴细胞的行为，导致其不适当的生存和保留。我们将这些观察扩展到另一种慢性持续性风湿病，即干燥综合征，并发现组成型 B 细胞吸引趋化因子 BCA-1 (CXCL13) 的异位产生与淋巴细胞积累和淋巴组织形成相关。这些发现表明，成纤维细胞等基质细胞通过允许淋巴细胞在错误的时间积聚在错误的位置，在从急性消退到慢性持续性关节炎的转变中发挥着重要作用。
Chronic inflammation is characterized by the accumulation of leucocytes within tissues. In rheumatoid arthritis the inflammatory infiltrate shares many architectural features with lymphoid tissue. For example, CD4 T cells and B cells accumulate in perivascular lymphoid structures within synovial tissue. CD8 T cells and neutrophils are found predominantly within synovial fluid. What drives these distinctive lymphoid microstructures and the relative contribution of lymphocytes and stromal cells such as fibroblasts to this process is the subject of this review. Cellular interactions between leucocytes and stromal cells such as macrophages and fibroblasts are important in generating tumour necrosis factor-alpha within the inflamed synovium. Therefore understanding how leucocytes accumulate within the inflamed synovium is likely to provide new therapeutic approaches to modify the inflammatory process. We have found that fibroblasts play a dominant role in defining the disordered synovial microenvironment in rheumatoid arthritis. Through their production of a variety of cytokines (interferon-beta, transforming growth factor-beta) and constitutive chemokines (stromal cell-derived factor-1, CXCL12) they directly alter the behaviour of lymphocytes that accumulate within chronically inflamed joints leading to their inappropriate survival and retention. We have extended these observations to another chronic persistent rheumatic disease, Sjogren's syndrome, and found that ectopic production of the constitutive B cell-attracting chemokine BCA-1 (CXCL13) is associated with lymphocyte accumulation and lymphoid tissue formation. These findings suggest that stromal cells such as fibroblasts play an important role in the switch from acute resolving to chronic persistent arthritis by allowing lymphocytes to accumulate in the wrong place at the wrong time.