Role of the chemokine stromal cell-derived factor 1 in autoantibody production and nephritis in murine lupus
Role of the chemokine stromal cell-derived factor 1 in autoantibody production and nephritis in murine lupus
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DOI：
10.4049/jimmunol.170.6.3392
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发表时间：
2003-03-15
影响因子：
4.4
通讯作者：
Emilie, D
中科院分区：
文献类型：
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作者：
Balabanian, K;Couderc, J;Emilie, D
在正常小鼠中，基质细胞衍生因子1 （SDF-1/CXCL12）促进腹膜B1a （PerB1a）淋巴细胞的迁移、增殖和存活。因为这些细胞表达。我们在新西兰黑/新西兰白（NZB/W）小鼠中测试了它们对SDF-1的反应。NZB/W小鼠的PerBla淋巴细胞对SDF-1异常敏感。这种更高的敏感性是由于NZB遗传背景，在其他B淋巴细胞亚群中没有观察到，并且是由IL-10调节的。SDF-1在腹腔和脾脏中组成性产生。在患有肾炎的NZB/W小鼠肾小球中足细胞也能产生。在生命早期给予SDF-1或IL-10拮抗剂可防止NZB/W小鼠自身抗体、肾炎和死亡的发生。在患有肾炎的小鼠中，在生命后期开始抗sdf -1单抗治疗，可以抑制自身抗体的产生，消除蛋白尿和Ig沉积，并逆转肾脏的形态变化。这种处理也抵消了B1a淋巴细胞的扩增和T淋巴细胞的活化。因此，在NZB/W小鼠中，PerBla淋巴细胞对SDF-1和IL-10的联合作用异常敏感，而SDF-1是狼疮小鼠模型中自身免疫发展的关键。
In normal mice, stromal cell-derived factor 1 (SDF-1/CXCL12) promotes the migration, proliferation, and survival of peritoneal B1a (PerB1a) lymphocytes. Because these cells express. a self-reactive repertoire and are expanded in New Zealand Black/New Zealand White (NZB/W) mice, we tested their response to SDF-1 in such mice. PerBla lymphocytes from NZB/W mice were exceedingly sensitive to SDF-1. This greater sensitivity was due to the NZB genetic background, it was not observed for other B lymphocyte subpopulations, and it was modulated by IL-10. SDF-1 was produced constitutively in the peritoneal cavity and in the spleen. It was also produced by podocytes in the glomeruli of NZB/W mice with nephritis. The administration of antagonists of either SDF-1 or IL-10 early in life prevented the development of autoantibodies, nephritis, and death in NZB/W mice. Initiation of anti-SDF-1 mAb treatment later in life, in mice with established nephritis, inhibited autoantibody production, abolished proteinuria and Ig deposition, and reversed morphological changes in the kidneys. This treatment also counteracted B1a lymphocyte expansion and T lymphocyte activation. Therefore, PerBla lymphocytes are abnormally sensitive to the combined action of SDF-1 and IL-10 in NZB/W mice, and SDF-1 is key in the development of autoimmunity in this murine model of lupus.