Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Department of Respiratory Medicine, The Third People's Hospital of Hefei, Hefei, China.
Front Immunol. 2022 Jun 10;13:898660. doi: 10.3389/fimmu.2022.898660. eCollection 2022.
pneumonia (PCP) is a common medical issue in immunosuppressive patients. Increasing evidence supports that B cells may play an essential role in PCP individuals. The present study aims to integrate lncRNA and mRNA expression profiles and further investigate the molecular function of mature B cells in PCP.
The lung tissue of wild-type (WT) mice and B-cell-activating factor receptor-deficient (mature B-cell deficiency, BAFF-R) mice were harvested at 3 weeks after being infected with pneumocystis. After total RNAs were extracted, transcriptome profiling was performed following the Illumina HiSeq 3000 protocol. lncRNA-targeted miRNA pairs were predicted using the online databases. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment pathways were analyzed to functionally annotate these differentially expressed genes. Additionally, the immune-related lncRNA-miRNA-mRNA-ceRNA network was subsequently performed. The quantitative real-time PCR (RT-PCR) analysis was conducted to evaluate the lncRNA and mRNA expression profiles in WT-PCP mice and BAFF-R PCP mice.
Compared with the control group, 166 mRNAs were observed to be aberrantly expressed (fold change value ≥2; 0.05) in the BAFF-R PCP group, including 39 upregulated and 127 downregulated genes, while there were 69 lncRNAs differently expressed in the BAFF-R PCP group, including 15 upregulated and 54 downregulated genes. In addition, GO and KEGG pathway analyses showed that BAFF-R deficiency played an important role in the primary and adaptive immune responses in PCP. Furthermore, the lncRNA and mRNA co-expression network was established. We noted that the core network of lncRNA-TF (transcription factor) pairs could be classified into the categories including infection and immunity pathways.
In summary, in this study, we further explored the role of mature B cells in the pathogenesis and progression of PCP and the data demonstrated that BAFF-R deficiency could play a significant role in immune regulation in the PCP population.
肺炎（PCP）是免疫抑制患者常见的医学问题。越来越多的证据表明 B 细胞可能在 PCP 个体中发挥重要作用。本研究旨在整合长链非编码 RNA（lncRNA）和信使 RNA（mRNA）表达谱，并进一步研究成熟 B 细胞在 PCP 中的分子功能。
在感染肺囊虫后 3 周，采集野生型（WT）小鼠和 B 细胞激活因子受体缺陷（成熟 B 细胞缺乏，BAFF-R）小鼠的肺组织。提取总 RNA 后，按照 Illumina HiSeq 3000 方案进行转录组谱分析。使用在线数据库预测 lncRNA 靶向 miRNA 对。对这些差异表达基因进行京都基因与基因组百科全书（KEGG）和基因本体论（GO）富集途径分析，以进行功能注释。此外，还进行了免疫相关的 lncRNA-miRNA-mRNA-ceRNA 网络分析。通过定量实时 PCR（RT-PCR）分析评估 WT-PCP 小鼠和 BAFF-R PCP 小鼠的 lncRNA 和 mRNA 表达谱。
与对照组相比，BAFF-R PCP 组有 166 个 mRNAs（fold change value≥2; 0.05）表达异常，包括 39 个上调和 127 个下调基因，而 BAFF-R PCP 组有 69 个 lncRNAs 表达不同，包括 15 个上调和 54 个下调基因。此外，GO 和 KEGG 通路分析表明，BAFF-R 缺乏在 PCP 的原发性和适应性免疫反应中起重要作用。此外，建立了 lncRNA-mRNA 共表达网络。我们注意到，lncRNA-TF（转录因子）对的核心网络可分为感染和免疫途径类别。
综上所述，本研究进一步探讨了成熟 B 细胞在 PCP 发病机制和进展中的作用，数据表明 BAFF-R 缺乏在 PCP 人群的免疫调节中可能发挥重要作用。
