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Publication Detail
Agrin signalling contributes to cell activation and is overexpressed in T lymphocytes from lupus patients
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Jury EC, Eldridge J, Isenberg DA, Kabouridis PS
  • Publication date:
    01/12/2007
  • Pagination:
    7975, 7983
  • Journal:
    Journal of Immunology
  • Volume:
    179
  • Issue:
    11
  • Status:
    Published
  • Print ISSN:
    0022-1767
Abstract
It 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-α, 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-α 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-α, and may have an important function during cell activation with potential implications for autoimmunity. Copyright © 2007 by The American Association of Immunologists, Inc.
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