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长链非编码 RNA 参与了疫苗接种反应中的多种免疫途径。

Long noncoding RNAs are involved in multiple immunological pathways in response to vaccination.

机构信息

Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, 05508-000 São Paulo, Brazil.

Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, 8380492 Santiago, Chile.

出版信息

Proc Natl Acad Sci U S A. 2019 Aug 20;116(34):17121-17126. doi: 10.1073/pnas.1822046116. Epub 2019 Aug 9.

Abstract

Understanding the mechanisms of vaccine-elicited protection contributes to the development of new vaccines. The emerging field of systems vaccinology provides detailed information on host responses to vaccination and has been successfully applied to study the molecular mechanisms of several vaccines. Long noncoding RNAs (lncRNAs) are crucially involved in multiple biological processes, but their role in vaccine-induced immunity has not been explored. We performed an analysis of over 2,000 blood transcriptome samples from 17 vaccine cohorts to identify lncRNAs potentially involved with antibody responses to influenza and yellow fever vaccines. We have created an online database where all results from this analysis can be accessed easily. We found that lncRNAs participate in distinct immunological pathways related to vaccine-elicited responses. Among them, we showed that the expression of lncRNA FAM30A was high in B cells and correlates with the expression of immunoglobulin genes located in its genomic vicinity. We also identified altered expression of these lncRNAs in RNA-sequencing (RNA-seq) data from a cohort of children following immunization with intranasal live attenuated influenza vaccine, suggesting a common role across several diverse vaccines. Taken together, these findings provide evidence that lncRNAs have a significant impact on immune responses induced by vaccination.

摘要

了解疫苗引起的保护机制有助于开发新疫苗。新兴的系统疫苗学领域提供了宿主对疫苗接种反应的详细信息,并已成功应用于研究几种疫苗的分子机制。长非编码 RNA(lncRNA)在多种生物过程中起着至关重要的作用,但它们在疫苗引起的免疫中的作用尚未得到探索。我们对来自 17 个疫苗队列的超过 2000 个血液转录组样本进行了分析,以鉴定可能与流感和黄热病疫苗抗体反应相关的 lncRNA。我们创建了一个在线数据库,其中可以轻松访问此分析的所有结果。我们发现 lncRNA 参与了与疫苗引起的反应相关的不同免疫途径。其中,我们表明 lncRNA FAM30A 在 B 细胞中表达较高,并且与位于其基因组附近的免疫球蛋白基因的表达相关。我们还在接种鼻内减毒活流感疫苗的儿童的 RNA 测序(RNA-seq)数据中鉴定到这些 lncRNA 的表达发生了改变,这表明它们在几种不同疫苗中具有共同作用。总之,这些发现提供了证据表明 lncRNA 对疫苗引起的免疫反应有重大影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ad9/6708379/3efe41f42b34/pnas.1822046116fig01.jpg

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