Immunologic Research

, Volume 57, Issue 1, pp 3–11

Immunobiology of TNFSF15 and TNFRSF25

Immunology & Microbiology in Miami

DOI: 10.1007/s12026-013-8465-0

Cite this article as:
Schreiber, T.H. & Podack, E.R. Immunol Res (2013) 57: 3. doi:10.1007/s12026-013-8465-0


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.


TNFSF15TNFRSF25TL1ADR3FoxP3TregT cellCostimulationAdjuvantImmunotherapy

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Microbiology and ImmunologyUniversity of Miami Miller School of MedicineMiamiUSA