The TNF-family cytokine TL1A inhibits proliferation of human activated B cells

PLoS One. 2013;8(4):e60136. doi: 10.1371/journal.pone.0060136. Epub 2013 Apr 2.


Death receptor (DR3) 3 is a member of the TNFR superfamily. Its ligand is TNF-like ligand 1A (TL1A), a member of the TNF superfamily. TL1A/DR3 interactions have been reported to modulate the functions of T cells, NK, and NKT cells and play a crucial role in driving inflammatory processes in several T-cell-dependent autoimmune diseases. However, TL1A expression and effects on B cells remain largely unknown. In this study, we described for the first time that B cells from human blood express significant amounts of DR3 in response to B cell receptor polyclonal stimulation. The relevance of these results has been confirmed by immunofluorescence analysis in tonsil and spleen tissue specimens, which showed the in situ expression of DR3 in antigen-stimulated B cells in vivo. Remarkably, we demonstrated that TL1A reduces B-cell proliferation induced by anti-IgM-antibodies and IL-2 but did not affect B-cell survival, suggesting that TL1A inhibits the signal(s) important for B-cell proliferation. These results revealed a novel function of TL1A in modulating B-cell proliferation in vitro and suggest that TL1A may contribute to homeostasis of effector B-cell functions in immune response and host defense, thus supporting the role of the TL1A/DR3 functional axis in modulating the adaptive immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Humans
  • Immunophenotyping
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Activation / immunology*
  • Palatine Tonsil / immunology
  • Palatine Tonsil / metabolism
  • Receptors, Tumor Necrosis Factor, Member 25 / metabolism
  • Tumor Necrosis Factor Ligand Superfamily Member 15 / pharmacology*


  • Antigens, CD
  • Receptors, Tumor Necrosis Factor, Member 25
  • TNFRSF25 protein, human
  • TNFSF15 protein, human
  • Tumor Necrosis Factor Ligand Superfamily Member 15

Grants and funding

This study was granted by Fondazione Cassa di Risparmio di Verona, Vicenza, Belluno e Ancona and Associazione Italiana Ricerca sul Cancro (AIRC) (grant #6599) and Fondazione Cassa di Risparmio di Verona, Vicenza, Belluno, e Ancona (grant #2008.14.44). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.