Immunobiology of TNFSF15 and TNFRSF25.
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.
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA, tschreibs@gmail.com.
Taylor H
TH
Schreiber
Eckhard R
ER
Podack
D056704:Adaptive Immunity / Q000502:physiology; D000818:Animals; D006801:Humans; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D053219:Receptors, Tumor Necrosis Factor, Member 25; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15