Siglec-G Deficiency Leads to More Severe Collagen-Induced Arthritis and Earlier Onset of Lupus-like Symptoms in MRL/lpr Mice
Siglec-G Deficiency Leads to More Severe Collagen-Induced Arthritis and Earlier Onset of Lupus-like Symptoms in MRL/lpr Mice
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DOI：
10.4049/jimmunol.1303367
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发表时间：
2014-04-01
影响因子：
4.4
通讯作者：
Nitschke, Lars
中科院分区：
文献类型：
--
作者：
Boekers, Susanne;Urbat, Anne;Nitschke, Lars
Siglec- g是唾液酸结合igg样凝集素（Siglec）家族的成员，在所有B细胞上表达。siglece - g缺陷小鼠显示出B1细胞区室的大量扩张，证明了siglece - g作为抑制受体在该细胞亚群中的关键作用。虽然Siglec- g缺陷小鼠不会产生自发自身免疫，但Siglec- g和相关Siglec蛋白CD22双缺陷小鼠在老年时确实表现出自身免疫。在这项研究中，我们探讨了sigleg本身的缺失是否会影响类风湿关节炎和系统性红斑狼疮动物模型的疾病严重程度。与对照组小鼠相比，siglecg缺陷小鼠在胶原诱导关节炎后表现出中度加重的临床严重程度和更高的膝关节炎症。siglecg缺陷小鼠也回交到自身免疫易感性MLR/lpr背景。尽管siglece - g缺陷小鼠和对照MRL/lpr小鼠均出现狼疮样疾病，但siglece - g缺陷MRL/lpr小鼠表现出更早的自身抗体发生；淋巴细胞B细胞和T细胞增生；早期发病，如蛋白尿和肾小球损伤所示。此外，与雌性对照MRL/lpr小鼠相比，siglecg缺陷雌性小鼠的存活率显著降低。因此，抑制受体siglece - g的缺失导致MRL/lpr小鼠中胶原诱导的关节炎和自发性狼疮肾炎的疾病严重程度中度加重和早期发病。
Siglec-G is a member of the sialic acid-binding Ig-like lectin (Siglec) family expressed on all B cells. Siglec-G-deficient mice show a large expansion of the B1 cell compartment, demonstrating the crucial role of Siglec-G as an inhibitory receptor on this cellular subset. Although Siglec-G-deficient mice did not develop spontaneous autoimmunity, mice double-deficient for Siglec-G and the related Siglec protein CD22 did show autoimmunity at an older age. In this study, we addressed the question of whether loss of Siglec G on its own affects disease severity in animal models of rheumatoid arthritis and systemic lupus erythematosus. Siglec-G-deficient mice showed moderately increased clinical severity and higher inflammation of the knee joints following collagen-induced arthritis, when compared with control mice. The Siglec-G-deficient mouse was also backcrossed to the autoimmune prone MLR/lpr background. Although both Siglec-G-deficient and control MRL/lpr mice developed a lupus-like disease, Siglec-G-deficient MRL/lpr mice showed an earlier occurrence of autoantibodies; a higher lymphoproliferation of B and T cells; and an earlier onset of disease, as shown by proteinuria and glomerular damage in the kidney. Moreover, Siglec-G-deficient female mice showed a significantly reduced survival compared with female control MRL/lpr mice. Thus, the loss of the inhibitory receptor Siglec-G led to a moderate exacerbation of disease severity and early onset in both collagen-induced arthritis and spontaneous lupus nephritis in MRL/lpr mice.