Genetic variation at the CD28 locus and its impact on expansion of pro-inflammatory CD28 negative T cells in healthy individuals.

Liaskou, Evaggelia and Jeffery, Louisa and Chanouzas, Dimitrios and Soskic, Blagoje and Seldin, Michael F and Harper, Lorraine and Sansom, David and Hirschfield, Gideon M (2017) Genetic variation at the CD28 locus and its impact on expansion of pro-inflammatory CD28 negative T cells in healthy individuals. Scientific reports, 7 (1). p. 7652. ISSN 2045-2322. This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs

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Official URL: https://www.nature.com/articles/s41598-017-07967-2

Abstract

The CD28 locus is associated with susceptibility to a variety of autoimmune and immune-mediated inflammatory diseases including primary sclerosing cholangitis (PSC). Previously, we linked the CD28 pathway in PSC disease pathology and found that vitamin D could maintain CD28 expression. Here, we assessed whether the PSC-associated CD28 risk variant A (rs7426056) affects CD28 expression and T cell function in healthy individuals (n = 14 AA, n = 14 AG, n = 14 GG). Homozygotes for the PSC disease risk allele (AA) showed significantly lower CD28 mRNA expression ex-vivo than either GG or AG (p < 0.001) in total peripheral blood mononuclear cells. However, the CD28 risk variant alone was not sufficient to explain CD28 protein loss on CD4 T cells. All genotypes responded equally to vitamin D as indicated by induction of a regulatory phenotype and an increased anti-inflammatory/pro-inflammatory cytokine ratio. A genotypic effect on response to TNFα stimuli was detected, which was inhibited by vitamin D. Together our results show: (a) an altered gene expression in carriers of the susceptible CD28 variant, (b) no differences in protein levels on CD4 T cells, and

Item Type: Article
Additional Information: This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs
Subjects: QZ Pathology. Oncology
Divisions: Clinical Support
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Depositing User: Miss Emily Johnson
Date Deposited: 04 Mar 2019 15:28
Last Modified: 04 Mar 2019 15:28
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/1898

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