Identification of Pancreatic Glycoprotein 2 as an Endogenous Immunomodulator of Innate and Adaptive Immune Responses

被引：55

作者：

Werner, Lael ^{[1
]}

Paclik, Daniela ^{[1
]}

Fritz, Christina ^{[2
]}

Reinhold, Dirk ^{[3
]}

Roggenbuck, Dirk ^{[2
]}

Sturm, Andreas ^{[1
]}

机构：

[1] Med Univ Berlin, Charite Campus Virchow Clin, Dept Med, Div Gastroenterol & Hepatol, D-13353 Berlin, Germany

[2] Medipan GmbH, D-15827 Dahlewitz, Germany

[3] Univ Magdeburg, Inst Mol & Clin Immunol, D-39106 Magdeburg, Germany

来源：

JOURNAL OF IMMUNOLOGY | 2012年 / 189卷 / 06期

关键词：

GRANULE MEMBRANE-PROTEIN; INFLAMMATORY-BOWEL-DISEASE; TAMM-HORSFALL PROTEIN; T-CELLS; ANCHORED PROTEINS; PREGNANCY URINE; CROHNS-DISEASE; GP2; ANTIBODIES; UROMODULIN;

D O I：

10.4049/jimmunol.1103190

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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-alpha 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. The Journal of Immunology, 2012, 189: 2774-2783.

引用

页码：2774 / 2783

页数：10

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