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首页> 外文期刊>The Journal of Immunology: Official Journal of the American Association of Immunologists >Role of the chemokine stromal cell-derived factor 1 in autoantibody production and nephritis in murine lupus.
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Role of the chemokine stromal cell-derived factor 1 in autoantibody production and nephritis in murine lupus.

机译:趋化因子基质细胞衍生因子1在鼠狼疮自身抗体产生和肾炎中的作用。

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摘要

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. PerB1a 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, PerB1a 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.
机译: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。因为这些细胞表达自我反应的库,并在新西兰黑/新西兰白(NZB / W)小鼠中扩增,所以我们在此类小鼠中测试了它们对SDF-1的反应。 NZB / W小鼠的PerB1a淋巴细胞对SDF-1非常敏感。这种更高的敏感性归因于NZB遗传背景,其他B淋巴细胞亚群未观察到这种敏感性,并且被IL-10调节。 SDF-1在腹膜腔和脾脏中组成性产生。它也由患有肾炎的NZB / W小鼠肾小球的足细胞产生。在生命早期给予SDF-1或IL-10拮抗剂可预防NZB / W小鼠自身抗体的发展,肾炎和死亡。在患有肾炎的小鼠中,在生命后期开始抗SDF-1 mAb治疗,抑制自身抗体产生,消除蛋白尿和Ig沉积,并逆转肾脏的形态变化。该治疗还抵消了B1a淋巴细胞的扩增和T淋巴细胞的活化。因此,PerB1a淋巴细胞对NZB / W小鼠中SDF-1和IL-10的联合作用异常敏感,而SDF-1在这种狼疮鼠模型中自身免疫发展的关键。

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