Immunobiology of TNFSF15 and TNFRSF25

Taylor H. Schreiber, Eckhard R. Podack

Research output: Contribution to journalArticle

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3-11
Number of pages9
JournalImmunologic Research
Volume57
Issue number1-3
DOIs
StatePublished - Dec 1 2013

Keywords

  • Adjuvant
  • Costimulation
  • DR3
  • FoxP3
  • Immunotherapy
  • T cell
  • TL1A
  • TNFRSF25
  • TNFSF15
  • Treg

ASJC Scopus subject areas

  • Immunology

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