Tissue transglutaminase treatment leads to concentration-dependent changes in dendritic cell phenotype - implications for the role of transglutaminase in coeliac disease

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.Dendritic cells (DCs) are part of the innate immune system with a vital role in modulating adaptive immune responses [1,2]. DCs have a life cycle consisting of two distinct phases [2]. In the immature state, they act as sentinels and are particularly concentrated in areas of microbial exposure, where they take up and process antigens for presentation by MHC molecules [3]. Once activated, 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 T-helper (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. [2,4]. DCs are particularly important for the induction of na？ve Th responses owing to their abundant surface expression of co-stimulatory molecules such as CD80 and CD86 [3-5]. DCs are also thought to play an important role in inducing and controlling tolerance in the periphery [6]. 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 ph