Dataset Information

CD8αα⁺T cells exert a pro-inflammatory role in patients with psoriasis.

ABSTRACT:

Background

Psoriasis is a common chronic inflammatory disease caused by excessive activation of CD4⁺T cells, including Th17, Th1 and Th22. The role of CD8⁺T cells in psoriasis pathogenesis remains poorly understood.

Aim

To identify the phenotype of CD8⁺T cells in patients with psoriasis and to investigate its role in the formation of lesions.

Methods

The phenotype of CD8⁺T cells in psoriatic lesions was detected by immunofluorescence staining. Flow cytometry was performed to detect their phenotype in peripheral blood. Thereafter, coculture of CD8αα⁺T cells with autogenous CD4⁺T cells was performed to investigate the function of CD8αα⁺T cells in patients with psoriasis. Finally, pro-inflammatory factors produced by CD8αα⁺T cells were examined by immunofluorescence staining and flow cytometry.

Results

Compared to the CD8αβ⁺T cells, CD8αα⁺T cell infiltration in psoriatic lesions markedly increased. Moreover, epidermal CD8αα⁺T cells exhibited tissue-resident memory T cells (T_RM) phenotypes and dermal CD8αα⁺T cells exhibited effector memory (T_EM) phenotypes in psoriatic lesions. Additionally, we found that CD8αα⁺T cells from patients with psoriasis did not express the markers of regulatory T cells and could promote the proliferation of CD4⁺T effector cells and produce interleukin-17 and interferon-γ.

Conclusions

Our findings demonstrate that CD8αα⁺T cells contribute to the pathogenesis of psoriasis by producing pro-inflammatory factors.

SUBMITTER: Zhang YY

PROVIDER: S-EPMC9060015 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

CD8αα<sup>+</sup>T cells exert a pro-inflammatory role in patients with psoriasis.

Zhang Y Y YY Lin Y T YT Wang L L Sun X W XW Dang E L EL Xue K K Zhang W G WG Zhang K M KM Wang G G Li B B

Skin health and disease 20211116 4

<h4>Background</h4>Psoriasis is a common chronic inflammatory disease caused by excessive activation of CD4<sup>+</sup>T cells, including Th17, Th1 and Th22. The role of CD8<sup>+</sup>T cells in psoriasis pathogenesis remains poorly understood.<h4>Aim</h4>To identify the phenotype of CD8<sup>+</sup>T cells in patients with psoriasis and to investigate its role in the formation of lesions.<h4>Methods</h4>The phenotype of CD8<sup>+</sup>T cells in psoriatic lesions was detected by immunofluoresce ...[more]

PMID: 35663772

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Project description:BackgroundPsoriasis is an autoimmune/inflammatory disorder primarily affecting the skin. Chronic joint inflammation triggers the diagnosis of psoriatic arthritis (PsA) in approximately one-third of psoriasis patients. Although joint disease typically follows the onset of skin psoriasis, in around 15% of cases it is the initial presentation, which can result in diagnostic delays. The pathophysiological mechanisms underlying psoriasis and PsA are not yet fully understood, but there is evidence pointing towards epigenetic dysregulation involving CD4+ and CD8+ T-cells.ObjectivesThe aim of this study was to investigate disease-associated DNA methylation patterns in CD4+ T-cells from psoriasis and PsA patients that may represent potential diagnostic and/or prognostic biomarkers.MethodsPBMCs were collected from 12 patients with chronic plaque psoriasis and 8 PsA patients, and 8 healthy controls. CD4+ T-cells were separated through FACS sorting, and DNA methylation profiling was performed (Illumina EPIC850K arrays). Bioinformatic analyses, including gene ontology (GO) and KEGG pathway analysis, were performed using R. To identify genes under the control of interferon (IFN), the Interferome database was consulted, and DNA Methylation Scores were calculated.ResultsNumbers and proportions of CD4+ T-cell subsets (naïve, central memory, effector memory, CD45RA re-expressing effector memory cells) did not vary between controls, skin psoriasis and PsA patients. 883 differentially methylated positions (DMPs) affecting 548 genes were identified between controls and "all" psoriasis patients. Principal component and partial least-squares discriminant analysis separated controls from skin psoriasis and PsA patients. GO analysis considering promoter DMPs delivered hypermethylation of genes involved in "regulation of wound healing, spreading of epidermal cells", "negative regulation of cell-substrate junction organization" and "negative regulation of focal adhesion assembly". Comparing controls and "all" psoriasis, a majority of DMPs mapped to IFN-related genes (69.2%). Notably, DNA methylation profiles also distinguished skin psoriasis from PsA patients (2,949 DMPs/1,084 genes) through genes affecting "cAMP-dependent protein kinase inhibitor activity" and "cAMP-dependent protein kinase regulator activity". Treatment with cytokine inhibitors (IL-17/TNF) corrected DNA methylation patterns of IL-17/TNF-associated genes, and methylation scores correlated with skin disease activity scores (PASI).ConclusionDNA methylation profiles in CD4+ T-cells discriminate between skin psoriasis and PsA. DNA methylation signatures may be applied for quantification of disease activity and patient stratification towards individualized treatment.

Dataset Information

CD8αα⁺T cells exert a pro-inflammatory role in patients with psoriasis.

Background

Aim

Methods

Results

Conclusions

Publications

CD8αα<sup>+</sup>T cells exert a pro-inflammatory role in patients with psoriasis.

Similar Datasets

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Tweets

Dataset Information

CD8αα+T cells exert a pro-inflammatory role in patients with psoriasis.

Background

Aim

Methods

Results

Conclusions

Publications

CD8αα<sup>+</sup>T cells exert a pro-inflammatory role in patients with psoriasis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

CD8αα⁺T cells exert a pro-inflammatory role in patients with psoriasis.