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

Cell Immunol. 2014 May-Jun;289(1-2):55-62. doi: 10.1016/j.cellimm.2014.03.008. Epub 2014 Mar 31.

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.

Keywords: DC–T cell interaction; Dendritic cell; T cell activation; Transglutaminase 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antigens, CD / biosynthesis
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • B7-1 Antigen / biosynthesis
  • B7-2 Antigen / biosynthesis
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / immunology
  • CD40 Antigens / biosynthesis
  • Cell Communication / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • Dendritic Cells / enzymology
  • Dendritic Cells / immunology*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Histocompatibility Antigens Class II / biosynthesis
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-12 / metabolism
  • Interleukin-2 Receptor alpha Subunit / biosynthesis
  • Lectins, C-Type / biosynthesis
  • Lymphocyte Activation / immunology*
  • Lymphocyte Culture Test, Mixed
  • Male
  • Mice
  • Mice, Knockout
  • Protein Glutamine gamma Glutamyltransferase 2
  • T-Lymphocytes / immunology*
  • Transglutaminases / genetics
  • Transglutaminases / metabolism*

Substances

  • Antibodies
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • B7-1 Antigen
  • B7-2 Antigen
  • CD40 Antigens
  • CD69 antigen
  • Cd86 protein, mouse
  • Histocompatibility Antigens Class II
  • IL10 protein, mouse
  • Il2ra protein, mouse
  • Interleukin-2 Receptor alpha Subunit
  • Lectins, C-Type
  • Interleukin-10
  • Interleukin-12
  • Interferon-gamma
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins