Dataset Information

Comparative Study of Senescent Th Biomarkers in Healthy Donors and Early Arthritis Patients. Analysis of VPAC Receptors and Their Influence.

ABSTRACT: Pro-inflammatory CD4⁺CD28^- T cells are characteristic of immunosenescence, but also of several autoimmune/inflammatory diseases. Vasoactive intestinal peptide (VIP) acts as an anti-inflammatory and immunomodulatory mediator on these cells. Our objective was to study the mutual influence between senescent Th cells and VIP axis in early arthritis (EA), comparing with non-EA donors. We characterized the correlation between senescent Th cells and clinic parameters of EA as well as the behavior of senescent Th biomarkers by real-time PCR. Clinical data were systematically recorded at baseline and after 6 months of follow-up. The number of CD4⁺CD28^- T cells measured by sorting is higher in patients who initially meet ACR classification criteria for rheumatoid arthritis (RA) compared to those who were classified as undifferentiated arthritis (UA). A slight positive correlation between EA CD4⁺CD28^- T cells and CRP or ESR and a negative correlation with bone mineral density were found. Th senescent biomarkers in EA CD4⁺CD28^- T cells were similar to donors, however some of them increased after 6 months of follow-up. VPAC receptors were analyzed by real-time PCR and immunofluorescence, and CD4⁺CD28^- T cells showed higher expression of VPAC₂ and lower of VPAC₁, VPAC₂ showing a significant increased expression in EA cells. Sorted CD4⁺CD28^- T cells were in vitro expanded in presence of VIP, wherein VIP increased senescent biomarker CD27, while it diminished CD57 or NKG2 senescent biomarkers. Our study demonstrates for the first time the existence of a link between senescent Th cells and the VIP axis.

SUBMITTER: Villanueva-Romero R

PROVIDER: S-EPMC7761848 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Comparative Study of Senescent Th Biomarkers in Healthy Donors and Early Arthritis Patients. Analysis of VPAC Receptors and Their Influence.

Villanueva-Romero Raúl R Lamana Amalia A Flores-Santamaría Marissa M Carrión Mar M Pérez-García Selene S Triguero-Martínez Ana A Tomero Eva E Criado Gabriel G Pablos José L JL González-Álvaro Isidoro I Martínez Carmen C Juarranz Yasmina Y Gomariz Rosa P RP Gutiérrez-Cañas Irene I

Cells 20201204 12

Pro-inflammatory CD4<sup>+</sup>CD28<sup>-</sup> T cells are characteristic of immunosenescence, but also of several autoimmune/inflammatory diseases. Vasoactive intestinal peptide (VIP) acts as an anti-inflammatory and immunomodulatory mediator on these cells. Our objective was to study the mutual influence between senescent Th cells and VIP axis in early arthritis (EA), comparing with non-EA donors. We characterized the correlation between senescent Th cells and clinic parameters of EA as well ...[more]

PMID: 33291545

Similar Datasets

Project description:Excessive exposure to ultraviolet (UV) light is known to induce photoaging in the skin, necessitating the development of effective anti-photoaging strategies to mitigate the adverse effects of UV radiation. Understanding the biofunctional characteristics of diverse skin cell types and unraveling the molecular modifications implicated in the aging process are pivotal in comprehending the intricacies of photoaging in human skin. Such insights are essential for paving the way for innovative interventions to counteract the deleterious impact of UV radiation on the skin. The single-cell RNA sequencing data of UVB-irradiated and normal control mouse skin in GSE173385 were downloaded from the Gene Expression Omniniub (GEO) database. First, cell types were identified using Seurat for normalization, dimensionality reduction and clustering. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were executed on these cell subpopulations. Using FindAllMarkers in the Seurat package to identify differential gene expression and Monocle2 cell trajectory analysis, we screened out hub genes related to the development trajectory of senescent fibroblasts during photoaging, and then combined it with 307 aging-related genes collected in the HAGR library, we finally identified two biomarkers. The efficiency of biomarkers in diagnosing UV radiation photoaging was also evaluated in the dataset. Concurrently, the immune infiltration of identified biomarkers under UV radiation has also been further explored. Moreover, we employed the Enrichr platform to conduct a comprehensive screening of drug molecules associated with the identified biomarkers. Our comprehensive analysis, employing Seurat for normalization, dimensionality reduction, and clustering, successfully identified ten distinct cell types within the samples. Then GO functional enrichment analysis showed that senescent fibroblasts are mainly involved in the regulation of immune effector processes such as cytokine-mediated signaling pathways, regulation of epithelial cell proliferation and intercellular adhesion. Afterwards, KEGG analysis determined the main biological pathways are: IL-17 signaling pathway, Cytokine-cytokine receptor interaction, Metabolism of xenobiotics by cytochrome P450. After differential gene expression and Monocle2 cell trajectory analysis, we matched the obtained hub genes with the aging-related genes collected in the HAGR library, and finally screened out two relevant biomarkers: Apoe and Gdf15 which are related to the development trajectory of senescent fibroblasts during photoaging. Meanwhile, the immune infiltration further implied that the expression of these two biomarkers was significantly correlated with immune cells. In addition, the Enrichr platform was used to screen the drug molecules related to these biomarkers. This strategic approach aimed to pinpoint effective molecular targets for the prevention and treatment of photoaging. Our investigation has effectively characterized biomarkers associated with fibroblast senescence during photoaging at the single-cell level, We have validated their correlation with cellular immune inflammation and identified potential drug targets through the utilization of the Enrichr platform. This foundational research establishes a robust basis for the development of therapeutic interventions targeting skin diseases resulting from photoaging.

Dataset Information

Comparative Study of Senescent Th Biomarkers in Healthy Donors and Early Arthritis Patients. Analysis of VPAC Receptors and Their Influence.

Publications

Comparative Study of Senescent Th Biomarkers in Healthy Donors and Early Arthritis Patients. Analysis of VPAC Receptors and Their Influence.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets