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J Immunol. 2012 Sep 15;189(6):2774-83. doi: 10.4049/jimmunol.1103190. Epub 2012 Aug 13.

Identification of pancreatic glycoprotein 2 as an endogenous immunomodulator of innate and adaptive immune responses.

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  • 1Division of Hepatology and Gastroenterology, Department of Medicine, Charité-Campus Virchow Clinic, Medical University of Berlin, 13353 Berlin, Germany.

Abstract

Pancreatic autoantibodies are Crohn disease-specific serologic markers. The function and immunological role of their recently identified autoantigen, glycoprotein 2 (GP2), are unknown. We therefore investigated the impact of GP2 on modulation of innate and adaptive immune responses to evaluate its potential therapeutic use in mucosal inflammation. Our data indicate a previously unknown function for GP2 as an immunomodulator. GP2 was ubiquitously expressed on cells vital to mucosal immune responses. The expression of GP2 was upregulated on activated human T cells, and it was further influenced by pharmaceutical TNF-α inhibitors. Recombinant GP2 significantly decreased human intestinal epithelial cells, mucosal and peripheral T cell proliferation, apoptosis, and activation, and it distinctly modulated cytokine secretion. Furthermore, intestinal epithelial cells stimulated with GP2 potently attracted T cells. In conclusion, we demonstrate a novel role for GP2 in immune regulation that could provide a platform for new therapeutic interventions in the treatment of Crohn disease.

PMID:
22891285
[PubMed - indexed for MEDLINE]
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