Transglutaminase 2 is expressed and active on the surface of human monocyte-derived dendritic cells and macrophages.
The multifunctional enzyme, transglutaminase 2 (TG2), can be found intracellularly, in the extracellular matrix and on the cell surface. Cell surface TG2 (csTG2) could not be detected by TG2-specific antibodies or autoantibodies on immunocompetent cells. A supposedly csTG2-specific antibody, 6B9, was recently shown to actually react with CD44. Though the importance of TG2-mediated deamidation of gluten in the pathogenesis of celiac disease has been well recognized, it is not known in which intestinal cells or cell compartment the deamidation occurs. Duodenal dendritic cells (DCs) can be directly involved in gluten-reactive T-cell activation. Here we use blood monocyte-derived dendritic cells (iDC) and macrophages (MPhi) as a model for intestinal antigen-presenting cells (APCs) and show that they contain large amounts of TG2. We found that TG100, a commercial TG2-specific monoclonal antibody can recognize TG2 on the surface of these cells, that is monocyte-derived APCs express surface-associated TG2. TG2 expression was found on the surface of individual tunica propria cells in frozen small bowel tissue sections from both normal and celiac subjects. We also demonstrate that the pool of TG2 on the surface of iDCs can be catalytically active, hence it might directly be involved in the deamidation of gliadin peptides. Bacterial lipopolysaccharide (LPS) increased the level of TG2 on the surface of maturing DCs, supporting the hypothesis that an unspecific inflammatory process in the gut may expose more transglutaminase activity.
Hodrea
Judit
J
Department of Biochemistry and Molecular Biology, Hungarian Academy of Sciences, University of Debrecen, Debrecen, Hungary.
Demény
Máté A
MA
Majai
Gyöngyike
G
Sarang
Zsolt
Z
Korponay-Szabó
Ilma Rita
IR
Fésüs
László
L
D000818:Animals; D003713:Dendritic Cells / Q000737:chemistry / Q000201:enzymology* / Q000276:immunology*; D005434:Flow Cytometry; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008264:Macrophages / Q000737:chemistry / Q000201:enzymology* / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000737:chemistry / Q000378:metabolism*
D008565:Membrane Proteins; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins