16 research outputs found

    Reduced CD26bright expression of peripheral blood CD8+ T-cell subsets in psoriatic patients.

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    Contains fulltext : 71239.pdf (publisher's version ) (Closed access)Background: T cells have been shown to be highly relevant in psoriasis. CD26 is a novel T-cell activation marker involved in various T-cell functions, e.g. (i) co-stimulation, (ii) migration and (iii) T-cell memory response. In particular, CD26bright peripheral blood T cells have been shown to be altered in several autoimmune diseases. Objective: To characterize CD26-expression of T-cell subsets in psoriatic patients compared to healthy subjects. Methods: Peripheral blood was obtained from 15 untreated patients with severe psoriasis and from nine healthy subjects. The presence of specific CD26-related T-cell subsets was assessed by flow cytometry. Results: The CD26bright expression of CD8+ lymphocytes revealed a statistically significant (P<0.05) decrease in psoriatic patients. The majority of CD4+CD26bright cells are CD45RO+, whereas the minority of CD8+CD26bright cells are CD45RO+ in both groups. Conclusions: The present study demonstrates that the CD8CD26bright T-cell population is markedly decreased in peripheral blood of psoriatic patients. Moreover, CD26 expression did not show a restriction to memory T cells. As CD26 is of relevance for T-cell functions, future investigations should focus on elucidating these functions in psoriasis. It is attractive to speculate that the reduction in the CD8CD26bright subpopulation may represent a biomarker for recompartimentalization of activated T cells and a reduced CD8CD26bright count may correlate with increased responsiveness to T-cell targeted treatments

    A multi-omic analysis of human naïve CD4+ T cells

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    Background: Cellular function and diversity are orchestrated by complex interactions of fundamental biomolecules including DNA, RNA and proteins. Technological advances in genomics, epigenomics, transcriptomics and proteomics have enabled massively parallel and unbiased measurements. Such high-throughput technologies have been extensively used to carry out broad, unbiased studies, particularly in the context of human diseases. Nevertheless, a unified analysis of the genome, epigenome, transcriptome and proteome of a single human cell type to obtain a coherent view of the complex interplay between various biomolecules has not yet been undertaken. Here, we report the first multi-omic analysis of human primary naïve CD4+ T cells isolated from a single individual. Results: Integrating multi-omics datasets allowed us to investigate genome-wide methylation and its effect on mRNA/protein expression patterns, extent of RNA editing under normal physiological conditions and allele specific expression in naïve CD4+ T cells. In addition, we carried out a multi-omic comparative analysis of naïve with primary resting memory CD4+ T cells to identify molecular changes underlying T cell differentiation. This analysis provided mechanistic insights into how several molecules involved in T cell receptor signaling are regulated at the DNA, RNA and protein levels. Phosphoproteomics revealed downstream signaling events that regulate these two cellular states. Availability of multi-omics data from an identical genetic background also allowed us to employ novel proteogenomics approaches to identify individual-specific variants and putative novel protein coding regions in the human genome. Conclusions: We utilized multiple high-throughput technologies to derive a comprehensive profile of two primary human cell types, naïve CD4+ T cells and memory CD4+ T cells, from a single donor. Through vertical as well as horizontal integration of whole genome sequencing, methylation arrays, RNA-Seq, miRNA-Seq, proteomics, and phosphoproteomics, we derived an integrated and comparative map of these two closely related immune cells and identified potential molecular effectors of immune cell differentiation following antigen encounter
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