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.
Highlights
Dendritic cells (DCs) are part of the innate immune system with a vital role in modulating adaptive immune responses [1,2]
Transglutaminase increased DC endocytic ability and altered cell morphology Endocytic ability is key to the function of immature DCs, allowing capture of antigens for later presentation to T cells
The data in this study show that DCs cultured with transglutaminase 2 (TG-2) gained a different phenotype compared to control DCs, and compared to DCs treated with FN, a structural extracellular matrix (ECM) protein
Summary
Dendritic cells (DCs) are part of the innate immune system with a vital role in modulating adaptive immune responses [1,2]. By ligation of pattern-recognition receptors, they begin to mature and migrate to local lymph nodes [2] In lymph nodes, they present antigens to specific Thelper (Th) cells that, together with other factors such as cytokine microenvironment, determine the differentiation of T cells to one of several specialised subsets, such as Th1, Th2, Th17 or Treg. DCs are important for the induction of naïve Th responses owing to their abundant surface expression of co-stimulatory molecules such as CD80 and CD86 [3,4,5]. T cells that interact with immature DCs, which have low surface expression of co-stimulatory molecules [2], are likely to undergo apoptosis, become anergic (immunologically unresponsive) or differentiate to a regulatory phenotype [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
