Increased frequencies of circulating CXCL10-, CXCL8- and CCL4-producing monocytes and Siglec-3-expressing myeloid dendritic cells in systemic sclerosis patients

Carvalheiro, Tiago; Horta, Sara; Roon, Joël A G van; Santiago, Mariana; Salvador, Maria João; Trindade, Hélder; Radstake, Timothy R D J; Silva, José António Pereira da; Paiva, Artur

doi:10.1007/s00011-017-1106-7

Cited by 28 publications

(26 citation statements)

References 51 publications

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“…For example, the protein encoded by the IL8 gene is a member of the CXC chemokine family, is a major mediator of the inflammatory response and is also a potent angiogenic factor. It was shown that at diagnosis, increased levels of IL8 are detected in the cerebrospinal fluid (CSF) of MS patients with higher levels of gray matter damage (Carvalheiro et al, 2018;Magliozzi et al, 2018). Vascular endothelial growth factor A (VEGFA) is a member of the PDGF/VEGF growth factor family.…”

Section: Discussionmentioning

confidence: 99%

Identification of key genes associated with multiple sclerosis based on gene expression data from peripheral blood mononuclear cells

Shang

Sun

Zhang

et al. 2020

PeerJ

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The aim of this study was to identify the potential key candidate genes of multiple sclerosis (MS) and uncover mechanisms in MS. We combined data from the microarray expression profile of three MS stages and performed bioinformatics analysis. Differentially expressed genes (DEGs) were identified among the distinct stages of MS and healthy controls, and a total of 349 shared DEGs were identified. Gene ontology (GO) and pathway enrichment analyses showed that the DEGs were significantly enriched in the biological processes (BPs) of purine-related metabolic processes and signaling, especially the common DEGs, which were enriched in some immunological processes. Most of the DEGs were enriched in signaling pathways associated with the immune system, some immune diseases and infectious disease pathways. Through a protein–protein interaction (PPI) network analysis and a gene expression regulatory network constructed with MS-related miRNAs, we confirmed FOS, TP53, VEGFA, JUN, HIF1A, RB1, PTGS2, CXCL8, OAS2, NFKBIA and OAS1 as candidate genes of MS. Furthermore , we explored the potential SNPs associated with MS by database mining. In conclusion, this study provides the identified genes, SNPs, biological processes, and cellular pathways associated with MS. The uncovered candidate genes may be potential biomarkers involved in the diagnosis and therapy of MS.

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Section: Discussionmentioning

confidence: 99%

Identification of key genes associated with multiple sclerosis based on gene expression data from peripheral blood mononuclear cells

Shang

Sun

Zhang

et al. 2020

PeerJ

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“…As for CXCL10, markedly elevated protein levels were also detected in PBOV1 -overexpressed THP-1 supernatants. The pro-inflammatory chemokine CXCL10 has been reported to attract activated macrophages, T cells, and NK cells to the site of inflammation and is upregulated in autoimmune diseases, including RA [ 38 , 39 , 40 , 41 , 42 ]. It is suggested that CXCL10 increases the migration of inflammatory cells via CXCR3-mediated ERK activation and stimulates the production of osteoclastogenic cytokines in CD4+ T cells, resulting in bone destruction in RA [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

lncRNA NTT/PBOV1 Axis Promotes Monocyte Differentiation and Is Elevated in Rheumatoid Arthritis

Yang

Yen

et al. 2018

IJMS

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Monocytes/macrophages are important in orchestrating inflammatory responses. However, knowledge of the long noncoding RNA (lncRNA) regulation of monocytic cell differentiation and diseases remains limited. We aimed to elucidate the role of the 17 kb lncRNA noncoding transcript in T cells (NTT) in monocyte functions. Knockdown and chromatin immunoprecipitation (ChIP) assays in THP-1 cells (human monocytic leukemia cell line) revealed that NTT is regulated by the monocyte key transcription factor C/EBPβ and that it binds to the promoter of nearby gene PBOV1 via hnRNP-U. Overexpression of PBOV1 in THP-1 cells resulted in cell cycle G1 arrest, differentiation into macrophages, a marked increase in IL-10 and CXCL10 mRNA levels, and upregulation of the costimulatory molecules. In contrast to the downregulated NTT observed in lipopolysaccharide (LPS)-treated THP-1 cells, the C/EBPβ/NTT/PBOV1 axis was found to be hyperactivated in peripheral blood mononuclear cells (PBMCs) of first-time diagnosed untreated early rheumatoid arthritis (RA) patients, and their gene expression levels decreased markedly after treatment. Higher initial C/EBPβ/NTT/PBOV1 expression levels were associated with a trend of higher disease activity DAS28 scores. In conclusion, our study suggests that the lncRNA NTT is a regulator of inflammation in monocytes, and its activation participates in monocyte/macrophage differentiation and the pathogenesis of RA.

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“…In addition, they also produce more CXCL8 upon in‐vitro stimulation with lipopolysaccharide (LPS) plus IFN‐γ, which activate signalling pathways involved in SSc pathology. Moreover, dcSSc cDC2s were found to produce more CCL4 than cDC2 from healthy individuals . Differences in the cytokine production patterns may suggest differences in the molecular mechanism in two disease subtypes.…”

Section: Conventional Dcs and Inflammatory Dcs (Infldcs) In Sscmentioning

confidence: 96%

Novel insights into dendritic cells in the pathogenesis of systemic sclerosis

Carvalheiro

Zimmermann

Radstake

et al. 2020

Clinical and Experimental Immunology

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Summary Systemic sclerosis (SSc) is a severe autoimmune fibrotic disease characterized by fibrosis, vasculopathy, and immune dysregulation. Dendritic cells (DCs) are the most potent antigen‐presenting cells, specialized in pathogen sensing, with high capacity to shape the immune responses. The most recent technological advances have allowed the discovery of new DC subsets with potential implications in inflammatory conditions. Alterations of DC distribution in circulation and affected tissue as well as impaired DC function have been described in SSc patients, pointing towards a crucial role of these cells in SSc pathogenesis. In particular, recent studies have shown the importance of plasmacytoid DCs either by their high capacity to produce type I interferon or other inflammatory mediators implicated in SSc pathology, such as chemokine C‐X‐C motif ligand 4 (CXCL4). In‐vivo models of SSc have been vital to clarify the implications of DCs in this disease, especially DCs depletion and specific gene knock‐down studies. This review provides these new insights into the contribution of the different DCs subsets in the pathogenesis of SSc, as well as to the novel developments on DCs in in‐vivo models of SSc and the potential use of DCs and their mediators as therapeutic targets.

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Increased frequencies of circulating CXCL10-, CXCL8- and CCL4-producing monocytes and Siglec-3-expressing myeloid dendritic cells in systemic sclerosis patients

Cited by 28 publications

References 51 publications

Identification of key genes associated with multiple sclerosis based on gene expression data from peripheral blood mononuclear cells

Identification of key genes associated with multiple sclerosis based on gene expression data from peripheral blood mononuclear cells

lncRNA NTT/PBOV1 Axis Promotes Monocyte Differentiation and Is Elevated in Rheumatoid Arthritis

Novel insights into dendritic cells in the pathogenesis of systemic sclerosis

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