Marginal Zone B (MZB) Cells: Comparison of the Initial Identification of Immune Activity Leading to Dacryoadenitis and Sialadenitis in Experimental Sjögren's Syndrome.
Marginal Zone B (MZB) Cells: Comparison of the Initial Identification of Immune Activity Leading to Dacryoadenitis and Sialadenitis in Experimental Sjögren's Syndrome.
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DOI：
10.3390/ijms241512209
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发表时间：
2023-07-30
影响因子：
5.6
通讯作者：
Ambrus Jr, Julian L.
中科院分区：
文献类型：
--
作者：
Peck, Ammon B.;Ambrus Jr, Julian L.
关键词：
Sjögren’s综合征（SS）是一种人类系统性自身免疫性疾病，主要表现为泪腺和唾液腺功能的丧失。NOD/ShiLtJ系衍生的NOD- aec1aec2重组近交（RI）小鼠被认为是表现出人类疾病几乎所有特征的更合适的模型之一。该小鼠模型以及其他SS小鼠模型表明，B淋巴细胞对观察到的临床表现的发生和发展至关重要。最近，在C57BL/6进行了研究。IL14α转基因小鼠提供了明确的证据，表明边缘区B （MZB）细胞群直接参与了启动临床SS疾病发展的早期病理事件，以及导致B细胞淋巴瘤的晚期淋巴瘤发生。由于MZB细胞很难在体内和体外进行研究，我们进行了一系列的离体研究，利用时间全局RNA转录组学分析来分析在泪腺和唾液腺组织本身的病理生理事件的初始发作和随后发展过程中或与白细胞迁移到这些腺体相关的差异表达基因。最初的转录组学分析显示，虽然从泪腺和唾液腺获得的上调基因表达谱重叠，但在定义的激活途径之间存在多种遗传差异。在目前的研究中，我们提出了一个概念，表明两个腺体的初始病理事件不同，但随后激活1型干扰素信号的上调TLR4/TLR3信号转导通路在两个腺体中似乎是相同的，并表明对dsRNA（可能是病毒）的自身免疫反应。在这里，我们试图将这些发现纳入考虑范围，并确定它们如何影响未来治疗方案的设计。
Although multiple mouse strains have been advanced as models for Sjögren’s syndrome (SS), which is a human systemic autoimmune disease characterized primarily as the loss of lacrimal and salivary gland functions, the C57BL/6.NOD-Aec1Aec2 recombinant inbred (RI) mouse derived from the NOD/ShiLtJ line is considered one of the more appropriate models exhibiting virtually all the characteristics of the human disease. This mouse model, as well as other mouse models of SS, have shown that B lymphocytes are essential for the onset and development of observed clinical manifestations. Recently, studies carried out in the C57BL/6.IL14α transgenic mouse have provided clear evidence that the marginal zone B (MZB) cell population is directly involved in the early pathological events initiating the development of the clinical SS disease, as well as late-stage lymphomagenesis resulting in B-cell lymphomas. Since MZB cells are difficult to study in vivo and in vitro, we carried out a series of ex vivo investigations that utilize temporal global RNA transcriptomic analyses to profile differentially expressed genes exhibiting temporal upregulation during the initial onset and subsequent development of pathophysiological events within the lacrimal and salivary gland tissues per se or associated with the leukocyte cell migrations into these glands. The initial transcriptomic analyses revealed that while the upregulated gene expression profiles obtained from lacrimal and salivary glands overlap, multiple genetic differences exist between the defined activated pathways. In the current study, we present a concept suggesting that the initial pathological events differ between the two glands, yet the subsequent upregulated TLR4/TLR3 signal transduction pathway that activates the type-1 interferon signature appears to be identical in the two glands and indicates an autoimmune response against dsRNA, possibly a virus. Here, we attempt to put these findings into perspective and determine how they can impact the design of future therapeutic protocols.
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