Dr Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Davie, Florida.
Dr Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Davie, Florida.
PLoS One. 2022 Apr 21;17(4):e0266179. doi: 10.1371/journal.pone.0266179. eCollection 2022.
Mesenchymal stromal cells (MSCs) can be utilized clinically for treatment of conditions that result from excessive inflammation. In a pro-inflammatory environment, MSCs adopt an anti-inflammatory phenotype resulting in immunomodulation. A sub-type of MSCs referred to as "marrow-isolated adult multilineage inducible" (MIAMI) cells, which were isolated from bone marrow, were utilized to show that the addition of autophagy modulators, tamoxifen (TX) or chloroquine (CQ), can alter how MIAMI cells respond to IFNγ exposure in vitro resulting in an increased immunoregulatory capacity of the MIAMI cells. Molecularly, it was also shown that TX and CQ each alter both the levels of immunomodulatory genes and microRNAs which target such genes. However, the role of other non-coding RNAs (ncRNAs) such as long non-coding RNAs (lncRNAs) in regulating the response of MSCs to inflammation has been poorly studied. Here, we utilized transcriptomics and data mining to analyze the putative roles of various differentially regulated lncRNAs in MIAMI cells exposed to IFNγ with (or without) TX or CQ. The aim of this study was to investigate how the addition of TX and CQ alters lncRNA levels and evaluate how such changes could alter previously observed TX- and CQ-driven changes to the immunomodulatory properties of MIAMI cells. Data analysis revealed 693 long intergenic non-coding RNAS (lincRNAs), 480 pseudogenes, and 642 antisense RNAs that were differentially regulated with IFNγ, IFNγ+TX and IFNγ+CQ treatments. Further analysis of these RNA species based on the existing literature data revealed 6 antisense RNAs, 2 pseudogenes, and 5 lincRNAs that have the potential to modulate MIAMI cell's response to IFNγ treatment. Functional analysis of these genomic species based on current literature linking inflammatory response and ncRNAs indicated their potential for regulation of several key pro- and anti-inflammatory responses, including NFκB signaling, cytokine secretion and auto-immune responses. Overall, this work found potential involvement of multiple pro-and anti-inflammatory pathways and molecules in modulating MIAMI cells' response to inflammation.
间充质基质细胞（MSCs）可用于治疗因过度炎症引起的疾病。在促炎环境中，MSCs 采用抗炎表型，从而产生免疫调节作用。一种称为“骨髓分离的成年多谱系诱导”（MIAMI）的 MSC 亚类，从骨髓中分离出来，被用于证明添加自噬调节剂他莫昔芬（TX）或氯喹（CQ）可以改变 MIAMI 细胞在体外对 IFNγ 暴露的反应，从而增加 MIAMI 细胞的免疫调节能力。从分子水平上也表明，TX 和 CQ 各自改变了免疫调节基因和针对这些基因的 microRNAs 的水平。然而，其他非编码 RNA（ncRNA），如长非编码 RNA（lncRNA）在调节 MSC 对炎症的反应中的作用尚未得到充分研究。在这里，我们利用转录组学和数据挖掘来分析在 IFNγ （或 IFNγ+TX 或 IFNγ+CQ）存在的情况下，MIAMI 细胞中各种差异调节的 lncRNA 的可能作用。本研究的目的是研究添加 TX 和 CQ 如何改变 lncRNA 水平，并评估这种变化如何改变先前观察到的 TX 和 CQ 对 MIAMI 细胞免疫调节特性的驱动变化。数据分析显示，有 693 个长基因间非编码 RNA（lincRNA）、480 个假基因和 642 个反义 RNA 与 IFNγ、IFNγ+TX 和 IFNγ+CQ 处理相关。根据现有文献数据进一步分析这些 RNA 种类，发现有 6 个反义 RNA、2 个假基因和 5 个 lincRNA 具有调节 MIAMI 细胞对 IFNγ 治疗反应的潜力。根据目前文献中关于炎症反应和 ncRNA 的联系，对这些基因组物种的功能分析表明，它们可能调节几个关键的促炎和抗炎反应，包括 NFκB 信号、细胞因子分泌和自身免疫反应。总的来说，这项工作发现了多个促炎和抗炎途径和分子在调节 MIAMI 细胞对炎症反应中的潜在作用。
