B-cell maturation antigen, a proliferation-inducing ligand, and B-cell activating factor are candidate mediators of spinal cord injury-induced autoimmunity.
B-cell maturation antigen, a proliferation-inducing ligand, and B-cell activating factor are candidate mediators of spinal cord injury-induced autoimmunity.
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DOI：
10.1089/neu.2012.2501
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发表时间：
2013-04
影响因子：
4.2
通讯作者：
Jonah W Saltzman;R. Battaglino;L. Salles;P. Jha;Supreetha Sudhakar;E. Garshick;H. Stott;R. Zafonte;L. Morse
中科院分区：
文献类型：
--
作者：
Jonah W Saltzman;R. Battaglino;L. Salles;P. Jha;Supreetha Sudhakar;E. Garshick;H. Stott;R. Zafonte;L. Morse
自身免疫被认为是脊髓损伤（SCI）后不良神经预后的原因之一。然而，很少有基于机制的疗法，旨在减少脊髓损伤后的组织损伤和神经毒性，因为脊髓损伤诱导自身免疫的分子和细胞基础尚不完全清楚。最近在啮齿动物中的突破性研究表明，B细胞负责sci诱导的自身免疫。如果在人类身上得到证实，这种新模式将有助于设计神经保护免疫疗法。本研究的目的是研究脊髓损伤后自身免疫诱导的分子信号通路和机制，目的是确定旨在减少脊髓损伤慢性期组织损伤和炎症的治疗的潜在靶点。为此，我们对外周血单个核细胞进行了探索性微阵列分析，以鉴定慢性脊髓损伤中差异表达的基因。我们发现了一个与淋巴组织结构和发育相关的基因网络，该基因网络由29种不同的分子和5种蛋白质复合物组成，包括两种细胞因子，一种增殖诱导配体（APRIL）和B细胞活化因子（BAFF），以及一种受体，B细胞成熟抗原（BMCA），参与B细胞的发育、增殖、活化和存活。核糖核酸样品的实时聚合酶链反应分析证实这三个基因在脊髓损伤中表达上调。据我们所知，这是首次报道慢性脊髓损伤患者外周血单个核细胞产生BAFF和APRIL水平升高。这一发现为脊髓损伤后自身免疫系统通过APRIL和BAFF介导的B细胞活化提供了证据，并指出这些分子是减少脊髓损伤后神经炎症治疗的潜在靶点。
Autoimmunity is thought to contribute to poor neurological outcomes after spinal cord injury (SCI). There are few mechanism-based therapies, however, designed to reduce tissue damage and neurotoxicity after SCI because the molecular and cellular bases for SCI-induced autoimmunity are not completely understood. Recent groundbreaking studies in rodents indicate that B cells are responsible for SCI-induced autoimmunity. This novel paradigm, if confirmed in humans, could aid in the design of neuroprotective immunotherapies. The aim of this study was to investigate the molecular signaling pathways and mechanisms by which autoimmunity is induced after SCI, with the goal of identifying potential targets in therapies designed to reduce tissue damage and inflammation in the chronic phase of SCI. To that end, we performed an exploratory microarray analysis of peripheral blood mononuclear cells to identify differentially expressed genes in chronic SCI. We identified a gene network associated with lymphoid tissue structure and development that was composed of 29 distinct molecules and five protein complexes, including two cytokines, a proliferation-inducing ligand (APRIL) and B-cell-activating factor (BAFF), and one receptor, B-cell maturation antigen (BMCA) involved in B cell development, proliferation, activation, and survival. Real-time polymerase chain reaction analysis from ribonucleic acid samples confirmed upregulation of these three genes in SCI. To our knowledge, this is the first report that peripheral blood mononuclear cells produce increased levels of BAFF and APRIL in chronic SCI. This finding provides evidence of systemic regulation of SCI-autoimmunity via APRIL and BAFF mediated activation of B cells through BMCA and points toward these molecules as potential targets of therapies designed to reduce neuroinflammation after SCI.