Identification of pancreatic glycoprotein 2 as an endogenous immunomodulator of innate and adaptive immune responses.
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.
Division of Hepatology and Gastroenterology, Department of Medicine, Charité-Campus Virchow Clinic, Medical University of Berlin, 13353 Berlin, Germany.
Lael
L
Werner
Daniela
D
Paclik
Christina
C
Fritz
Dirk
D
Reinhold
Dirk
D
Roggenbuck
Andreas
A
Sturm
D056704:Adaptive Immunity; D001324:Autoantigens / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000276:immunology / Q000628:therapy; D003424:Crohn Disease / Q000276:immunology* / Q000628:therapy*; D058851:GPI-Linked Proteins / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D007155:Immunologic Factors / Q000502:physiology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism
D001324:Autoantigens; C489339:GP2 protein, human; D058851:GPI-Linked Proteins; D007155:Immunologic Factors