Upregulated Chemokine and Rho-GTPase Genes Define Immune Cell Emigration into Salivary Glands of Sjögren's Syndrome-Susceptible C57BL/6.NOD-Aec1Aec2 Mice.

Upregulated Chemokine and Rho-GTPase Genes Define Immune Cell Emigration into Salivary Glands of Sjögren's Syndrome-Susceptible C57BL/6.NOD-Aec1Aec2 Mice.
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DOI:
10.3390/ijms22137176
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发表时间:
2021-07-02
影响因子:
5.6
通讯作者:
Ambrus JL
Ambrus JL
中科院分区:
生物学2区
文献类型:
--
作者:
Peck AB;Nguyen CQ;Ambrus JL

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C57 BL/6. NOD-Aec 1Aec 2小鼠被认为是舍格伦综合征(SS)的非常合适的模型,舍格伦综合征是一种主要特征为泪腺和唾液腺功能丧失的人全身性自身免疫疾病。该小鼠模型以及SS的其他小鼠模型已经表明,B淋巴细胞对于观察到的临床表现的发展和发作是必不可少的。最近,在C57 BL/6. IL 14 α转基因小鼠中进行的研究表明,边缘区B(MZ B)细胞群与SS疾病的发生有关,反映了最近的观察结果,即MZ B细胞存在于SS患者的唾液腺中,并且最有可能引发随后的外分泌功能丧失。虽然MZB细胞很难在体内和体外研究,我们已经进行了离体调查,使用时间的全球RNA转录组学分析,以配置文件差异表达的基因已知与细胞迁移。结果表明C57 BL/6. NOD-Aec 1Aec 2小鼠唾液腺中特异性趋化因子、趋化因子受体和Rho-GT3基因的暂时上调与导管周围淋巴细胞浸润的早期出现相关。利用转录组学分析的力量来更好地定义淋巴细胞迁移到SS小鼠唾液腺的遗传特征,对SS疾病发展和发作的潜在机制的新见解开始成为焦点,从而为在细胞水平上进一步深入和新颖地研究SS疾病的隐蔽和早期明显阶段奠定了基础。
The C57BL/6.NOD-Aec1Aec2 mouse is considered a highly appropriate model of Sjögren’s Syndrome (SS), a human systemic autoimmune disease characterized primarily as the loss of lacrimal and salivary gland functions. This mouse model, as well as other mouse models of SS, have shown that B lymphocytes are essential for the development and onset of observed clinical manifestations. More recently, studies carried out in the C57BL/6.IL14α transgenic mouse have indicated that the marginal zone B (MZB) cell population is responsible for development of SS disease, reflecting recent observations that MZB cells are present in the salivary glands of SS patients and most likely initiate the subsequent loss of exocrine functions. Although MZB cells are difficult to study in vivo and in vitro, we have carried out an ex vivo investigation that uses temporal global RNA transcriptomic analyses to profile differentially expressed genes known to be associated with cell migration. Results indicate a temporal upregulation of specific chemokine, chemokine receptor, and Rho-GTPase genes in the salivary glands of C57BL/6.NOD-Aec1Aec2 mice that correlate with the early appearance of periductal lymphocyte infiltrations. Using the power of transcriptomic analyses to better define the genetic profile of lymphocytic emigration into the salivary glands of SS mice, new insights into the underlying mechanisms of SS disease development and onset begin to come into focus, thereby establishing a foundation for further in-depth and novel investigations of the covert and early overt phases of SS disease at the cellular level.
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