Mesenchymal Stem Cells Alleviate Inflammatory Bowel Disease Via Tr1 Cells.

Mesenchymal stem cells (MSCs) have been used to achieve exciting therapeutic outcomes in many animal studies and clinical trials for various autoimmune diseases, including inflammatory bowel disease (IBD). Type 1 regulatory T (Tr1) cells are the main source of interleukin (IL) 10 in the intestine. Whether Tr1 cells are involved during MSC-mediated IBD treatment is unclear. We treated a murine model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis with human umbilical cord-derived MSCs (hUCMSCs) and found that the disease severity was alleviated significantly in a dose-dependent manner. hUCMSCs increased the proportion of Tr1 cells and decreased that of T helper (Th)-1 and Th17 cells in the spleen and mesenteric lymph nodes in different stages of colitis. We found that the upregulation of Tr1 cells by hUCMSCs was abrogated after blocking indoleamine-2,3-dioxygenase (IDO), and IDO knockdown in hUCMSCs reversed the increase in Tr1 cell proportions caused by hUCMSCs in colitis. Moreover, hUCMSCs inhibited apoptosis and promoted the proliferation of Tr1 cells. Our results suggest that Tr1 cells play an important role in the amelioration of IBD by MSCs, and they are the target population for the alleviation of IBD by MSCs, providing meaningful references for the study of therapeutic mechanisms of MSCs in other inflammatory diseases.

Correlation Between Immune Lymphoid Cells and Plasmacytoid Dendritic Cells in Human Colon Cancer.

Background: Innate lymphoid cells (ILCs), so far studied mostly in mouse models, are important tissue-resident innate immune cells that play important roles in the colorectal cancer microenvironment and maintain mucosal tissue homeostasis. Plasmacytoid dendritic cells (pDCs) present complexity in various tumor types and are correlated with poor prognosis. pDCs can promote HIV-1-induced group 3 ILC (ILC3) depletion through the CD95 pathway. However, the role of ILC3s in human colon cancer and their correlation with other immune cells, especially pDCs, remain unclear. Methods: We characterized ILCs and pDCs in the tumor microenvironment of 58 colon cancer patients by flow cytometry and selected three patients for RNA sequencing. Results: ILC3s were negatively correlated, and pDCs were positively correlated, with cancer pathological stage. There was a negative correlation between the numbers of ILC3s and pDCs in tumor tissues. RNA sequencing confirmed the correlations between ILC3s and pDCs and highlighted the potential function of many ILC- and pDC-associated differentially expressed genes in the regulation of tumor immunity. pDCs can induce apoptosis of ILC3s through the CD95 pathway in the tumor-like microenvironment. Conclusions: One of the interactions between ILC3s and pDCs is via the CD95 pathway, which may help explain the role of ILC3s in colon cancer.

Comprehensive analysis of long non­coding RNA using an associated competitive endogenous RNA network in Wilms tumor.

Wilms tumor (WT) is the most common malignant renal neoplasm in children; however, the underlying molecular mechanisms are not well understood. According to the competing endogenous RNA (ceRNA) theory, long non­coding RNAs (lncRNAs) can regulate the expression of target genes by adsorbing microRNAs (miRNAs/miRs). However, the role of lncRNAs in WT has not been fully elucidated. The aim of the present study was to construct a ceRNA network to identify the potential lncRNAs involved in WT. The expression profiles of lncRNAs, miRNAs and mRNAs in 120 WT and six normal tissues were obtained from the Therapeutically Applicable Research to Generate Effective Treatments database. A total of 442 lncRNAs, 214 miRNAs and 4,912 mRNAs were identified as differentially expressed in WT and were enriched in 472 Gene Ontology terms (355 biological processes, 89 cellular components and 29 molecular functions) and 18 Kyoto Encyclopedia of Genes and Genomes pathways. A lncRNA­miRNA­mRNA ceRNA network of WT consisting of with 32 lncRNAs, 14 miRNAs and 158 mRNAs was constructed, based on the bioinformatics analysis of the miR target prediction database and the miRNAcode, miRTarBase and TargetScan databases. Subsequently, three lncRNAs, three miRNAs and 17 mRNAs, which had a significant effect on the overall survival rate of patients with WT, were identified based on the survival analysis. The three lncRNAs were also differentially expressed in the late and early stages of WT and were validated using the GSE66405 dataset obtained from the Gene Expression Omnibus database. In conclusion, the present study generated a specific lncRNA­related ceRNA network of WT, which may provide a novel perspective on the molecular mechanisms underlying the progression and prognosis of the disease.