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Immunobiology of TNFSF15 and TNFRSF25

  • Immunology & Microbiology in Miami
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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.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA

    Taylor H. Schreiber & Eckhard R. Podack

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  1. Taylor H. Schreiber
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  2. Eckhard R. Podack
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Correspondence to Taylor H. Schreiber.

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Schreiber, T.H., Podack, E.R. Immunobiology of TNFSF15 and TNFRSF25. Immunol Res 57, 3–11 (2013). https://doi.org/10.1007/s12026-013-8465-0

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  • DOI: https://doi.org/10.1007/s12026-013-8465-0

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