Death receptor 3

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is expressed preferentially by activated and antigen-experienced T lymphocytes. TNFRSF25 is also highly expressed by FoxP3 positive regulatory T lymphocytes. TNFRSF25 is activated by a monogamous ligand, known as TL1A (TNFSF15), which is rapidly upregulated in antigen presenting cells and some endothelial cells following Toll-Like Receptor or Fc receptor activation. This receptor has been shown to signal both through the TRADD adaptor molecule to stimulate NF-kappa B activity or through the FADD adaptor molecule to stimulate caspase activation and regulate cell apoptosis. == Therapeutics ==

Therapeutic agonists of TNFRSF25 can be used to stimulate Treg expansion, which can reduce inflammation in experimental models of asthma, allogeneic solid organ transplantation and ocular keratitis. Similarly, because TNFRSF25 activation is antigen dependent, costimulation of TNFRSF25 together with an autoantigen or with a vaccine antigen can lead to exacerbation of immunopathology or enhanced vaccine-stimulated immunity, respectively. TNFRSF25 stimulation is therefore highly specific to T cell mediated immunity, which can be used to enhance or dampen inflammation depending on the temporal context and quality of foreign vs self antigen availability. Stimulation of TNFRSF25 in humans may lead to similar, but more controllable, effects as coinhibitory receptor blockade targeting molecules such as CTLA-4 and PD-1. == References ==