Immunobiology of TNFSF15 and TNFRSF25

Immunol Res. 2013 Dec;57(1-3):3-11. doi: 10.1007/s12026-013-8465-0.

Abstract

TNFRSF25 is an understudied broad-acting T cell costimulator with high homology to TNFR1, however, the overall role of this receptor in T cell immunobiology is unclear. Ligation of TNFRSF25 by its monogamous ligand, TNFSF15 (TL1A), leads to recruitment of TNFR-associated factor 2 and TNFR-associated death domain in primary T cells with downstream activation of both NFκB as well as the PI3K/Akt axis. These signaling pathways are dependent upon coordinated engagement of the T cell receptor and interleukin-2 receptor and leads to the constitutive proliferation of CD4+FoxP3+ regulatory T cells (Treg) as a result of tonic exposure to self-antigen. Concurrent activation of CD4+ or CD8+ conventional T cell clones is dependent upon the availability of cognate foreign antigen. Here, we provide a review of both the literature and our work on this receptor and propose that the overall function of TL1A signaling to TNFRSF25 in T cells is to provide simultaneous costimulation of foreign-antigen-specific effector T cells and pre-existing Treg in order to focus the clonality of effector immunity to pathogen-derived antigens and reduce the risk of bystander inflammation toward self- or endogenous microbial antigens.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity / physiology
  • Animals
  • Humans
  • Receptors, Tumor Necrosis Factor, Member 25 / chemistry
  • Receptors, Tumor Necrosis Factor, Member 25 / genetics
  • Receptors, Tumor Necrosis Factor, Member 25 / metabolism*
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • Tumor Necrosis Factor Ligand Superfamily Member 15 / chemistry
  • Tumor Necrosis Factor Ligand Superfamily Member 15 / genetics
  • Tumor Necrosis Factor Ligand Superfamily Member 15 / metabolism*

Substances

  • Receptors, Tumor Necrosis Factor, Member 25
  • Tumor Necrosis Factor Ligand Superfamily Member 15