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TNF/TNFR Superfamily Members in Costimulation of T Cell Responses-Revisited.
Annu Rev Immunol
January 2025
Department of Immunology, University of Toronto, Toronto, Ontario, Canada; email:
Prosurvival tumor necrosis factor receptor (TNFR) superfamily (TNFRSF) members on T cells, including 4-1BB, CD27, GITR, and OX40, support T cell accumulation during clonal expansion, contributing to T cell memory. During viral infection, tumor necrosis factor superfamily (TNFSF) members on inflammatory monocyte-derived antigen-presenting cells (APCs) provide a postpriming signal (signal 4) for T cell accumulation, particularly in the tissues. Patients with loss-of-function mutations in TNFR/TNFSF members reveal a critical role for 4-1BB and CD27 in CD8 T cell control of Epstein-Barr virus and other childhood infections and of OX40 in CD4 T cell responses.
View Article and Find Full Text PDFStructure-activity relationship study of Pseudellone C as anti-glioma agents by targeting TNF/TNFR signaling pathway.
Eur J Med Chem
November 2024
Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China. Electronic address:
Glioma, a common primary brain tumor, is highly infiltrative and invasive, often leading to drug resistance and recurrence. Therefore, the development of novel therapeutic agents is urgently needed. Pseudellone C is a novel marine triindole alkaloid.
View Article and Find Full Text PDFDistinct Role of TNFR1 and TNFR2 in Protective Immunity Against Infection in Mice.
Front Immunol
April 2022
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, United States.
Infection with , an obligate intracellular bacterium, can cause mild or severe scrub typhus. Some patients develop acute lung injury, multi-organ failure, and fatal infection; however, little is known regarding key immune mediators that mediate infection control or disease pathogenesis. Using murine models of scrub typhus, we demonstrated in this study the requirement of TNF-TNFR signaling in protective immunity against this infection.
View Article and Find Full Text PDFCD95L Inhibition Impacts Gemcitabine-Mediated Effects and Non-Apoptotic Signaling of TNF-α and TRAIL in Pancreatic Tumor Cells.
Cancers (Basel)
October 2021
Institute for Experimental Cancer Research, University Medical Centre Schleswig-Holstein (UKSH), Campus Kiel, 24105 Kiel, Germany.
Despite the potential apoptotic functions, the CD95/CD95L system can stimulate survival as well as pro-inflammatory signaling, particularly through the activation of NFκB. This holds true for the TNF/TNFR and the TRAIL/TRAILR systems. Thus, signaling pathways of these three death ligands converge, yet the specific impact of the CD95/CD95L system in this crosstalk has not been well studied.
View Article and Find Full Text PDFAtypical TNF-TNFR superfamily binding interface in the GITR-GITRL complex for T cell activation.
Cell Rep
September 2021
Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address:
Glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) is a critical regulatory molecule in modulation of T cell immune responses. Here we report the mouse GITR (mGITR) and mGITR ligand (mGITRL) complex structure and find that the binding interface of mGITR and mGITRL is distinct from the typical tumor necrosis factor superfamily (TNFSF)/TNF receptor superfamily (TNFRSF) members. mGITR binds to its ligand with a single domain, whereas the binding interface on mGITRL is located on the side, which is distal from conserved binding sites of TNFSF molecules.
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