Transglutaminase 2 on the surface of dendritic cells is proposed to be involved in dendritic cell–T cell interaction

Abstract

Transglutaminase 2 (TG2) is a ubiquitous enzyme involved in diverse biological processes. Recently, its function in adaptive immune responses has begun to emerge. Its presence and functions in B cells and T cells, for example, have been reported. However, those in dendritic cells (DCs), the principal antigen-presenting cells, are as yet unexplored in murine system. In this study, we first investigated the expression of TG2 in murine bone marrow-derived DCs, and then compared the functioning of these cells in the presence or absence of this enzyme using wild-type (WT) and TG2−/− mice. We found that the WT DCs expressed TG2 both in the cytoplasm and on the cell surface, both of which were elevated after LPS stimulation. Unexpectedly, between WT and TG2−/− DCs, there were no remarkable differences in cytokine secretion, IL-10 and IL-12, and neither in the expression of surface molecules CD80, CD86, and MHC II, excepting a moderate decrease of CD40 expression on the TG2−/− DCs. However, when T cells were stimulated with TG2−/− DCs, they showed decreased levels of proliferation, CD69 and CD25 expression, and IFN-γ secretion. The addition of anti-TG2 antibody to the WT DC–T cell co-culture resulted in decreased T cell activation. By immunofluorescence staining, TG2 was observed at DC–T cell interface (contact point). Taken together, we propose that TG2 on the surface of DCs modulates the DC–T cell interaction.