Differential survival of leukocyte subsets mediated by synovial, bone marrow, and skin fibroblasts: site-specific versus activation-dependent survival of T cells and neutrophils.
Differential survival of leukocyte subsets mediated by synovial, bone marrow, and skin fibroblasts: site-specific versus activation-dependent survival of T cells and neutrophils.
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DOI：
10.1002/art.21930
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发表时间：
2006-07
影响因子：
--
通讯作者：
Buckley, Christopher D
中科院分区：
文献类型：
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作者：
Filer, Andrew;Parsonage, Greg;Smith, Emily;Osborne, Chloe;Thomas, Andrew M C;Curnow, S John;Rainger, G Ed;Raza, Karim;Nash, Gerard B;Lord, Janet;Salmon, Mike;Buckley, Christopher D
滑膜成纤维细胞与骨髓源性成纤维细胞有许多共同的表型标志。在这项研究中，我们研究了来自3个不同来源(骨髓、滑膜和皮肤)的匹配成纤维细胞的作用，以检验滑膜成纤维细胞在支持T细胞和中性粒细胞存活方面与骨髓来源成纤维细胞相似的假设。匹配的滑膜、骨髓和皮肤成纤维细胞取自8名接受膝关节或髋关节手术的不同类风湿性关节炎患者。将静息或激活的成纤维细胞与CD4T细胞或中性粒细胞共培养，检测白细胞存活、凋亡和增殖的程度。来自所有3个部位的成纤维细胞支持主要由干扰素-β介导的CD4T细胞的存活。然而，滑膜和骨髓成纤维细胞共享增强的部位特异性能力，在没有增殖的情况下维持CD4T细胞的存活，这种效应独立于成纤维细胞的激活或增殖，但需要T细胞和成纤维细胞的直接接触。相反，成纤维细胞介导的中性粒细胞存活效率较低，与成纤维细胞的来源无关，但依赖于成纤维细胞先前的激活，并且仅由可溶性因素介导，主要是粒细胞-巨噬细胞集落刺激因子。这些结果表明，成纤维细胞在各种组织微环境中白细胞亚群的差异积累中发挥着重要的功能作用。这一发现也为慢性炎症性疾病中观察到的T细胞和中性粒细胞聚集模式的部位特异性差异提供了潜在的解释。
Synovial fibroblasts share a number of phenotype markers with fibroblasts derived from bone marrow. In this study we investigated the role of matched fibroblasts obtained from 3 different sources (bone marrow, synovium, and skin) to test the hypothesis that synovial fibroblasts share similarities with bone marrow–derived fibroblasts in terms of their ability to support survival of T cells and neutrophils. Matched synovial, bone marrow, and skin fibroblasts were established from 8 different patients with rheumatoid arthritis who were undergoing knee or hip surgery. Resting or activated fibroblasts were cocultured with either CD4 T cells or neutrophils, and the degree of leukocyte survival, apoptosis, and proliferation were measured. Fibroblasts derived from all 3 sites supported increased survival of CD4 T cells, mediated principally by interferon-β. However, synovial and bone marrow fibroblasts shared an enhanced site-specific ability to maintain CD4 T cell survival in the absence of proliferation, an effect that was independent of fibroblast activation or proliferation but required direct T cell–fibroblast cell contact. In contrast, fibroblast-mediated neutrophil survival was less efficient, being independent of the site of origin of the fibroblast but dependent on prior fibroblast activation, and mediated solely by soluble factors, principally granulocyte–macrophage colony-stimulating factor. These results suggest an important functional role for fibroblasts in the differential accumulation of leukocyte subsets in a variety of tissue microenvironments. The findings also provide a potential explanation for site-specific differences in the pattern of T cell and neutrophil accumulation observed in chronic inflammatory diseases.