Abstract
BackgroundThe goals of this study were to explore the expression profiles and functional networks of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in mesenchymal stromal cells (MSCs) involved in regulating the function of monocytes and to clarify the mechanisms by which MSCs exert immunoregulatory effects on monocytes.MethodsMSCs and CD14+ monocytes were separately isolated. The immunoregulatory effects of MSCs on monocytes were determined by flow cytometry. lncRNAs and mRNAs that were differentially expressed (DE) between the control group (MSCs only) and co-culture group (MSCs co-cultured with monocytes) were identified through high-throughput sequencing and bioinformatic analyses and were confirmed by qRT-PCR. Bioinformatic analyses were performed to identify the critical biological functions and signalling pathways involved in MSC-mediated monocyte regulation and to identify the functional networks formed between DE mRNAs and lncRNAs.ResultsMSCs showed a strong ability to induce monocyte migration but inhibited monocyte differentiation into M1 macrophages. A total of 145 DE lncRNAs and 768 DE mRNAs were identified between the control and co-culture groups. Significant fold changes in lncRNAs and mRNAs were confirmed by qRT-PCR. GO analysis demonstrated that DE mRNAs and lncRNAs were highly associated with terms related to binding and biological regulation. KEGG analysis revealed 122 significantly regulated pathways, including the cytokine-cytokine receptor pathway and chemokine signalling pathway. Interaction and co-expression networks were constructed for DE mRNAs and lncRNAs, and several key microRNAs were identified in the competitive endogenous RNA (ceRNA) network. Target genes of the DE lncRNAs were analysed to predict critical mRNA-lncRNA axes involved in the immunoregulatory function of MSCs.ConclusionsOur research describes the lncRNA and mRNA expression profiles and functional networks involved in MSC-mediated regulation of monocytes. These results provide possible molecular mechanisms for the immunoregulatory function of MSCs and may help to elucidate possible molecular therapeutic targets in MSCs for the treatment of autoimmune diseases.
Highlights
The goals of this study were to explore the expression profiles and functional networks of long noncoding RNAs and messenger RNAs in mesenchymal stromal cells (MSCs) involved in regulating the function of monocytes and to clarify the mechanisms by which Mesenchymal stromal cell (MSC) exert immunoregulatory effects on monocytes
We demonstrated that the ratio of CD14+ monocytes that differentiated into M1
Several cytokines are contained within this list, including CCL8, CXCL6, CCL20, CXCL5, CXCL8 and CXCL3, which are secreted by MSCs and are important for regulating the function of CD14+ monocytes
Summary
The goals of this study were to explore the expression profiles and functional networks of long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) in mesenchymal stromal cells (MSCs) involved in regulating the function of monocytes and to clarify the mechanisms by which MSCs exert immunoregulatory effects on monocytes. Mesenchymal stromal cells (MSCs) are cells with multiple forms of differentiation potential and self-renewal ability [1]. These cells are derived from the mesoderm and play a role in regulating many types of immune cells [2], including monocytes [3, 4], dendritic cells [5] and T lymphocytes [6]. These powerful features contribute to their critical role in the clinical treatment of various diseases, such as systemic lupus erythaematosus (SLE) [7, 8] and graft-versus-host disease (GVDH) [9, 10]. A better understanding of these mechanisms may help to improve the curative effect of MSCs and illuminate the pathogenesis of autoimmune diseases
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