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Expression patterns of signaling lymphocytic activation molecule family members in peripheral blood mononuclear cell subsets in patients with systemic lupus erythematosus.

ABSTRACT: Genome-wide linkage analysis studies (GWAS) studies in systemic lupus erythematosus (SLE) identified the 1q23 region on human chromosome 1, containing the Signaling Lymphocytic Activation Molecule Family (SLAMF) cluster of genes, as a lupus susceptibility locus. The SLAMF molecules (SLAMF1-7) are immunoregulatory receptors expressed predominantly on hematopoietic cells. Activation of cells of the adaptive immune system is aberrant in SLE and dysregulated expression of certain SLAMF molecules has been reported. We examined the expression of SLAMF1-7 on peripheral blood T cells, B cells, monocytes, and their respective differentiated subsets, in patients with SLE and healthy controls in a systematic manner. SLAMF1 levels were increased on both T cell and B cells and their differentiated subpopulations in patients with SLE. SLAMF2 was increased on SLE CD4+ and CD8+ T cells. The frequency of SLAMF4+ and SLAMF7+ central memory and effector memory CD8+ T cells was reduced in SLE patients. Naïve CD4+ and CD8+ SLE T cells showed a slight increase in SLAMF3 levels. No differences were seen in the expression of SLAMF5 and SLAMF6 among SLE patients and healthy controls. Overall, the expression of various SLAMF receptors is dysregulated in SLE and may contribute to the immunopathogenesis of the disease.

SUBMITTER: Karampetsou MP

PROVIDER: S-EPMC5636110 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Expression patterns of signaling lymphocytic activation molecule family members in peripheral blood mononuclear cell subsets in patients with systemic lupus erythematosus.

Karampetsou Maria P MP Comte Denis D Kis-Toth Katalin K Kyttaris Vasileios C VC Tsokos George C GC

PloS one 20171011 10

Genome-wide linkage analysis studies (GWAS) studies in systemic lupus erythematosus (SLE) identified the 1q23 region on human chromosome 1, containing the Signaling Lymphocytic Activation Molecule Family (SLAMF) cluster of genes, as a lupus susceptibility locus. The SLAMF molecules (SLAMF1-7) are immunoregulatory receptors expressed predominantly on hematopoietic cells. Activation of cells of the adaptive immune system is aberrant in SLE and dysregulated expression of certain SLAMF molecules has ...[more]

PMID: 29020082

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Project description:BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease with a complicated pathogenesis, and its aetiology has not been clearly unveiled. The lack of effective diagnosis and treatment methods makes it necessary to explore the molecular mechanism of SLE. We aimed to identify some critical signalling pathways and key competing endogenous RNAs (ceRNAs) underlying the molecular mechanism of SLE and to map out the systematic signalling networks by integrating the data on different kinds of RNAs.MethodsPeripheral blood mononuclear cells (PBMCs) were collected from both SLE patients and healthy subjects, RNA was extracted from the PBMCs, and RNA libraries including ribosomal RNA-depleted strand-specific libraries and small RNA libraries were built for deep RNA sequencing (RNA-seq). RNA-seq yielded differential expression profiles of lncRNAs/circRNAs/miRNAs/mRNAs related to SLE. The DAVID database (v. 6.8) was employed for Gene Ontology (GO) and KEGG pathway analysis. ceRNA networks (circRNA/lncRNA-miRNA-mRNA) were constructed and visualized using Cytoscape software (v. 3.5.0). The TargetScan and miRanda databases were used to predict target relationships in ceRNA networks. qRT-PCR was used to verify our data.ResultsDifferential expression of ceRNAs related to SLE was detected in SLE patients' PBMCs: 644 mRNAs (384 upregulated, 260 downregulated), 326 miRNAs (223 upregulated, 103 downregulated), 221 lncRNAs (79 upregulated, 142 downregulated), and 31 circRNAs (21 upregulated, 10 downregulated). We drew ceRNA signalling networks made up of the differentially expressed mRNAs/miRNAs/lncRNAs/circRNAs mentioned above, and the hub genes included IRF5, IFNAR2, TLR7, IRAK4, STAT1, STAT2, C2, and Tyk2. These hub genes were involved in ceRNA signalling pathways, such as the IL-17 signalling pathway and type I interferon signalling pathway.ConclusionsWe explored the differential expression profiles of various kinds of ceRNAs and integrated signalling networks constructed by ceRNAs. Our findings offer new insights into the pathogenesis of SLE and hint at therapeutic strategies.

Project description:Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease, characterized by overactive inflammation and aberrant activation of lymphocytes. Chemokine C-X-C motif ligand 10 (CXCL10) has an important role in the initiation and deterioration of SLE. However, the expression levels of CXCL10 mRNA in T-helper (Th) cells and B lymphocytes from SLE patients have remained elusive. In the present study, a Bioinformatics analysis of differentially expressed gene (DEG) profiles obtained from RNA sequencing data for three matched samples was performed to explore the hub genes, mainly through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes and protein-protein interaction analysis. Furthermore, the expression of CXCL10 in peripheral blood mononuclear cells (PBMCs), CD4+ Th cells and CD19+ B cells of 108 subjects, including 66 SLE patients and 42 healthy controls, was confirmed by reverse transcription-quantitative PCR. In addition, 4 single-nucleotide polymorphism (SNP) loci in the 3'-untranslated region of CXCL10 were assessed using the Snapshot SNP genotyping assay. A total of 152 clustered DEGs mainly accumulated in immune-associated GO terms and interferon-associated pathways were identified. The expression of CXCL10, one of the central genes in the interaction network cluster (the degree of interaction, MCODE score=28.414), was 6.27-fold higher in SLE patients compared with control patients. Furthermore, CXCL10 mRNA was confirmed to be elevated in PBMCs and CD19+ B cells of patients with SLE (P<0.001 for the two cell types). However, no significant difference in CD4+ T lymphocytes was present (P=0.881). In addition, no polymorphism was identified in four selected loci from the samples. Taken together, the present results demonstrated that CXCL10, one of the hub genes in the pathogenesis of SLE, is upregulated in PBMCs and B lymphocytes of patients with SLE, although none of the SNPs selected for analysis in the present study were identified to have any potential associations with SLE.

Dataset Information

Expression patterns of signaling lymphocytic activation molecule family members in peripheral blood mononuclear cell subsets in patients with systemic lupus erythematosus.

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Expression patterns of signaling lymphocytic activation molecule family members in peripheral blood mononuclear cell subsets in patients with systemic lupus erythematosus.

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