Class A scavenger receptors regulate tolerance against apoptotic cells, and autoantibodies against these receptors are predictive of systemic lupus.
Class A scavenger receptors regulate tolerance against apoptotic cells, and autoantibodies against these receptors are predictive of systemic lupus.
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DOI：
10.1084/jem.20070600
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发表时间：
2007-10-01
期刊：
影响因子：
--
通讯作者：
Karlsson MC
中科院分区：
文献类型：
--
作者：
Wermeling F;Chen Y;Pikkarainen T;Scheynius A;Winqvist O;Izui S;Ravetch JV;Tryggvason K;Karlsson MC
凋亡细胞被认为是自身免疫性疾病（如系统性红斑狼疮，SLE）中自身抗原的主要来源。与此相符的是，凋亡细胞清除缺陷已被证明会增加疾病易感性。然而，对于凋亡细胞衍生的自身抗原如何激活自身反应性B细胞以及这一过程发生在何处，我们知之甚少。在这项研究中，我们发现凋亡细胞被脾边缘区巨噬细胞上表达的特定清道夫受体摄取，并且缺乏这些受体的小鼠自身抗体反应阈值较低。此外，在易患SLE的小鼠出现临床症状之前就发现了针对清道夫受体的抗体，在确诊的SLE患者中也发现了此类抗体。我们的研究结果描述了一种新的机制，即针对清道夫受体的自身抗体能够改变对凋亡细胞的反应，影响耐受性，从而促进疾病进展。由于在小鼠发病之前就能检测到自身抗体，它们可能具有作为SLE早期指标的预测价值。
Apoptotic cells are considered to be a major source for autoantigens in autoimmune diseases such as systemic lupus erythematosus (SLE). In agreement with this, defective clearance of apoptotic cells has been shown to increase disease susceptibility. Still, little is known about how apoptotic cell–derived self-antigens activate autoreactive B cells and where this takes place. In this study, we find that apoptotic cells are taken up by specific scavenger receptors expressed on macrophages in the splenic marginal zone and that mice deficient in these receptors have a lower threshold for autoantibody responses. Furthermore, antibodies against scavenger receptors are found before the onset of clinical symptoms in SLE-prone mice, and they are also found in diagnosed SLE patients. Our findings describe a novel mechanism where autoantibodies toward scavenger receptors can alter the response to apoptotic cells, affect tolerance, and thus promote disease progression. Because the autoantibodies can be detected before onset of disease in mice, they could have predictive value as early indicators of SLE.
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影响因子：
30.5
作者：
Guinamard, R;Okigaki, M;Ravetch, JV
通讯作者：
Ravetch, JV
DOI：
10.1016/s0074-7696(06)50005-1
发表时间：
2006
期刊：
International review of cytology
影响因子：
--
作者：
Kraal G;Mebius R
通讯作者：
Mebius R
DOI：
10.1084/jem.20030684
发表时间：
2003-07-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Karlsson MC;Guinamard R;Bolland S;Sankala M;Steinman RM;Ravetch JV
通讯作者：
Ravetch JV
DOI：
10.1084/jem.188.2.387
发表时间：
1998-07-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mevorach D;Zhou JL;Song X;Elkon KB
通讯作者：
Elkon KB
影响因子：
32.4
作者：
Bolland, S;Ravetch, JV
通讯作者：
Ravetch, JV