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Agrin signalling contributes to cell activation and is overexpressed in T lymphocytes from lupus patients

Jury, EC; Eldridge, J; Isenberg, DA; Kabouridis, PS; (2007) Agrin signalling contributes to cell activation and is overexpressed in T lymphocytes from lupus patients. J IMMUNOL , 179 (11) 7975 - 7983. Gold open access

Abstract

is shown in this study that the heparan sulfate proteoglycan agrin is overexpressed in T cells isolated from patients with the autoimmune disease systemic lupus erythematosus (SLE). Freshly isolated CD4(+) and CD8(+) subpopulations both exhibited higher expression over healthy controls, which however, gradually declined when cells were cultured in vitro. Agrin expression was induced following in vitro activation of cells via their Ag receptor, or after treatment with IFN-alpha, a cytokine shown to be pathogenic in lupus. Furthermore, serum from SLE patients with active disease was able to induce agrin expression when added to T cells from healthy donors, an increase that was partially blocked by neutralizing anti-IFN-alpha Abs. Cross-linking agrin with mAbs resulted in rapid reorganization of the actin cytoskeleton, activation of the ERK MAPK cascade, and augmentation of anti-CD3-induced proliferation and IL-10 production, indicating that agrin is a functional receptor in T cells. These results demonstrate that agrin expression in human T cells is regulated by cell activation and IFN-alpha, and may have an important function during cell activation with potential implications for autoinummity.

Type: Article
Title: Agrin signalling contributes to cell activation and is overexpressed in T lymphocytes from lupus patients
Open access status: An open access publication
Publisher version: http://ukpmc.ac.uk/abstract/MED/18025246
Keywords: IMMUNOLOGICAL SYNAPSE, RECEPTOR MICROCLUSTERS, ERYTHEMATOSUS, EXPRESSION, PROTEIN, INTERFERON, ALPHA, DISEASE, BLOOD, ACTIN
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: http://discovery.ucl.ac.uk/id/eprint/117037
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