Unconventional ligand activation of herpesvirus entry mediator signals cell survival
| Autor: | Marcos W. Steinberg, Satoshi Fukuyama, Klaus Pfeffer, Patricia G. Spear, Hideki Sanjo, Matthew G. Macauley, Paula S. Norris, Kenneth M. Murphy, Timothy C. Cheung, Claire D'Souza, Carl F. Ware, Mitchell Kronenberg, Lisa M. Oborne |
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| Rok vydání: | 2009 |
| Předmět: |
TRAF3
Herpesvirus entry mediator Cell Survival T-Lymphocytes medicine.medical_treatment T cell Immunoglobulins BTLA Biology GPI-Linked Proteins Ligands Lymphocyte Activation Cell Line Mice Viral Envelope Proteins Antigens CD medicine Animals Humans Receptors Immunologic Multidisciplinary RELB Transcription Factor RelA T lymphocyte Biological Sciences TNF Receptor-Associated Factor 2 Cytokine medicine.anatomical_structure Cancer research Signal transduction Receptors Tumor Necrosis Factor Member 14 Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 106:6244-6249 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | The herpesvirus entry mediator (HVEM; TNFRSF14) activates NF-κB through the canonical TNF-related cytokine LIGHT, serving as a costimulatory pathway during activation of T cells. HVEM also functions as a ligand for the Ig superfamily members B and T lymphocyte attenuator (BTLA) and CD160, both of which limit inflammatory responses initiated by T cells. Emerging evidence indicates BTLA also promotes T cell survival, but its structural differences from LIGHT intimate BTLA is unlikely to function as an activator of HVEM. We demonstrate here that BTLA, CD160, and herpes simplex virus envelope glycoprotein D (gD) function as activating ligands for HVEM, promoting NF-κB activation and cell survival. Membrane-expressed BTLA and CD160, as well as soluble dimeric receptor surrogates BTLA-Fc and gD-Fc specifically activated HVEM-dependent NF-κB. BTLA and CD160 engagement induced recruitment of TNF receptor-associated factor 2 (TRAF2), but not TRAF3, to HVEM that specifically activated the RelA but not the RelB form of NF-κB in a mucosal epithelial tumor cell line. Moreover, Btla −/− T cells survived poorly following activation but were rescued with BTLA-Fc, indicating HVEM-BTLA bidirectional signaling may serve as a critical cell-survival system for lymphoid and epithelial cells. |
| Databáze: | OpenAIRE |
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