Effect of Myd88 deficiency on gene expression profiling in salivary glands of female non-obese diabetic (NOD) mice
Effect of Myd88 deficiency on gene expression profiling in salivary glands of female non-obese diabetic (NOD) mice
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DOI：
10.1016/j.job.2021.04.003
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发表时间：
2021-06-07
影响因子：
2.4
通讯作者：
Into, Takeshi
中科院分区：
文献类型：
--
作者：
Mori, Taiki;Kataoka, Hideo;Into, Takeshi
目的：干燥综合征（Sj - oggren 's syndrome， SS）是一种慢性自身免疫性疾病，其特征是唾液腺和泪腺的炎性病变，由明显的淋巴细胞浸润引起。雌性非肥胖糖尿病小鼠（NOD）自发发生唾液腺炎性病变，具有ss样病理特征。先前的研究表明，MyD88是一种激活先天免疫信号的关键衔接蛋白，可影响淋巴细胞浸润，但其具体作用尚不清楚。在本研究中，我们通过基因表达谱研究了MyD88在雌性NOD小鼠唾液腺发病早期的作用。方法：采集10周龄雌性野生型和myd88缺失NOD小鼠的下颌腺进行RNA制备，并进行微阵列分析。分析微阵列数据集以鉴定myd88依赖性差异表达基因（DEGs）。生成的数据用于氧化石墨烯富集、KEGG通路、STRING数据库和INTERFEROME数据库分析。结果：发现Myd88缺乏影响230个deg，包括ss相关基因，如Cxcl9和Bpifa2。大多数deg被鉴定为参与免疫过程。KEGG通路分析表明，deg可能参与自身免疫性疾病，如系统性红斑狼疮和类风湿关节炎。此外，deg包含149个干扰素（IFN）调控基因。结论：MyD88参与NOD小鼠唾液腺中ifn相关免疫病理过程相关基因的表达。我们的发现对于理解myd88依赖性先天免疫信号在SS表现中的作用具有重要意义。(C) 2021日本口腔生物学协会。Elsevier B.V.版权所有。
Y Objectives: Sj ogren's syndrome (SS) is a chronic autoimmune disease characterized by inflammatory lesions in the salivary and lacrimal glands, which are caused by distinct lymphocytic infiltrates. Female non-obese diabetic (NOD) mice spontaneously develop inflammatory lesions of the salivary glands with SS-like pathological features. Previous studies have shown that MyD88, a crucial adaptor protein that activates innate immune signaling, affects lymphocytic infiltration, but its detailed role remains unclear. In this study, we investigated the role of MyD88 through gene expression profiling in the early phase of pathogenesis in the salivary glands of female NOD mice.Methods: Submandibular glands collected from 10-week-old female wild-type and Myd88-deficient NOD mice were used for RNA preparation, followed by microarray analysis. The microarray dataset was analyzed to identify Myd88-dependent differentially expressed genes (DEGs). Data generated were used for GO enrichment, KEGG pathway, STRING database, and INTERFEROME database analyses.Results: Myd88 deficiency was found to affect 230 DEGs, including SS-associated genes, such as Cxcl9 and Bpifa2. Most of the DEGs were identified as being involved in immunological processes. KEGG pathway analysis indicated that the DEGs were putatively involved in autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. Furthermore, the DEGs included 149 interferon (IFN)regulated genes.Conclusions: MyD88 is involved in the expression of specific genes associated with IFN-associated immunopathological processes in the salivary glands of NOD mice. Our findings are important for understanding the role of MyD88-dependent innate immune signaling in SS manifestation. (C) 2021 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.