Mannose-binding lectin blunts macrophage polarization and ameliorates lupus nephritis.
Mannose-binding lectin blunts macrophage polarization and ameliorates lupus nephritis.
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甘露糖结合凝集素减弱巨噬细胞极化并改善狼疮性肾炎
DOI：
10.1371/journal.pone.0062465
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Xiong S
中科院分区：
文献类型：
--
作者：
Cai Y;Zhang W;Xiong S
自身核抗原（包括DNA）清除缺陷是系统性红斑狼疮（SLE）的标志，SLE是一种慢性自身免疫性疾病，其特征是产生多种自身抗体、免疫复合物沉积以及严重的器官损伤。我们之前的研究表明，给同基因的BALB/c小鼠注射活化淋巴细胞来源的DNA（ALD - DNA）可诱发SLE疾病。甘露糖结合凝集素（MBL）是一种对DNA具有结合活性的分泌型模式识别受体，已被证明是炎症的调节因子，但MBL是否负责DNA清除、调节DNA介导的免疫反应以及是否参与DNA诱导的SLE疾病的发展仍知之甚少。
在ALD - DNA诱导的狼疮小鼠中，血清MBL水平显著降低，且与SLE疾病呈负相关。MBL通过抑制MAPK和NF - κB信号通路，同时增强CREB的激活，减弱巨噬细胞M2b极化。此外，MBL抑制了ALD - DNA刺激的巨噬细胞将T细胞极化为Th1细胞和Th17细胞的能力。重要的是，体内补充MBL可改善狼疮性肾炎。
这些结果表明，补充MBL可缓解SLE疾病，并可能暗示一种针对DNA诱导的SLE的潜在治疗策略，这将加深我们对MBL在SLE疾病中保护作用的理解。
Background Deficiency in clearance of self nuclear antigens, including DNA, is the hallmark of systemic lupus erythematosus (SLE), a chronic autoimmnue disease characterized by the production of various autoantibodies, immune complex deposition and severe organ damage. Our previous studies revealed that administration of syngeneic BALB/c mice with activated lymphocyte-derived DNA (ALD-DNA) could induce SLE disease. Mannose-binding lectin (MBL), a secreted pattern recognition receptor with binding activity to DNA, has been proved to be a modulator of inflammation, but whether MBL takes responsibility for DNA clearance, modulates the DNA-mediated immune responses, and is involved in the development of DNA-induced SLE disease remain poorly understood. Methodology/Principal Findings The levels of serum MBL significantly decreased in lupus mice induced by ALD-DNA and were negatively correlated with SLE disease. MBL blunted macrophage M2b polarization by inhibiting the MAPK and NF-κB signaling while enhancing the activation of CREB. Furthermore, MBL suppressed the ability of ALD-DNA–stimulated macrophages to polarize T cells toward Th1 cells and Th17 cells. Importantly, MBL supplement in vivo could ameliorate lupus nephritis. Conclusion/Significance These results suggest MBL supplement could alleviate SLE disease and might imply a potential therapeutic strategy for DNA-induced SLE, which would further our understanding of the protective role of MBL in SLE disease.
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