title: Tissue transglutaminase treatment leads to concentration-dependent changes in dendritic cell phenotype--implications for the role of transglutaminase in coeliac disease.
abstract: Dendritic cells (DCs) are part of the innate immune system with a key role in initiating and modulating T cell mediated immune responses. Coeliac disease is caused by inappropriate activation of such a response leading to small intestinal inflammation when gluten is ingested. Tissue transglutaminase, an extracellular matrix (ECM) protein, has an established role in coeliac disease; however, little work to date has examined its impact on DCs. The aim of this study was to investigate the effect of small intestinal ECM proteins, fibronectin (FN) and tissue transglutaminase 2 (TG-2), on human DCs by including these proteins in DC cultures.The study used flow cytometry and scanning electron microscopy to determine the effect of FN and TG-2 on phenotype, endocytic ability and and morphology of DCs. Furthermore, DCs treated with FN and TG-2 were cultured with T cells and subsequent T cell proliferation and cytokine profile was determined.The data indicate that transglutaminase affected DCs in a concentration-dependent manner. High concentrations were associated with a more mature phenotype and increased ability to stimulate T cells, while lower concentrations led to maintenance of an immature phenotype.These data provide support for an additional role for transglutaminase in coeliac disease and demonstrate the potential of in vitro modelling of coeliac disease pathogenesis.
authors.affiliation: Allergy and Tissue Modelling Research Group, School of Molecular Medical Sciences, Queen's Medical Centre, The University of Nottingham, A Floor, West Block, Nottingham, NG7 2UH, UK.
authors.forename: William J
authors.initials: WJ
authors.lastname: Dalleywater
authors.forename: David Y S
authors.initials: DY
authors.lastname: Chau
authors.forename: Amir M
authors.initials: AM
authors.lastname: Ghaemmaghami
mesh_terms: D002446:Celiac Disease / Q000201:enzymology* / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000201:enzymology* / Q000276:immunology; D004705:Endocytosis / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D010641:Phenotype; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D013601:T-Lymphocytes / Q000276:immunology; D011503:Transglutaminases / Q000494:pharmacology*
chemical_list: D016207:Cytokines; C000717608:TGM2 protein, human; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins