TY - JOUR UR - http://lib.ugent.be/catalog/pug01:1096147 ID - pug01:1096147 LA - eng TI - Polymorphic variants of LIGHT (TNF superfamily-14) alter receptor avidity and bioavailability PY - 2010 JO - (2010) JOURNAL OF IMMUNOLOGY SN - 0022-1767 PB - 2010 AU - Cheung, Timothy C AU - Coppieters, Ken GE01 001998188882 AU - Sanjo, Hideki AU - Oborne, Lisa M AU - Norris, Paula S AU - Coddington, Amy AU - Granger, Steven W AU - Elewaut, Dirk GE35 UZGent AU - Ware, Carl F AB - The TNF superfamily member homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for herpesvirus entry mediator (HVEM), a receptor expressed by T lymphocytes (LIGHT) [ TNF superfamily (SF)-14], is a key cytokine that activates T cells and dendritic cells and is implicated as a mediator of inflammatory, metabolic, and malignant diseases. LIGHT engages the lymphotoxin-beta receptor (LT beta R) and HVEM (TNFRSF14), but is competitively limited in activating these receptors by soluble decoy receptor-3 (DcR3; TNFRSF6B). Two variants in the human LIGHT alter the protein at E214K (rs344560) in the receptor-binding domain and S32L (rs2291667) in the cytosolic domain; however, the functional impact of these polymorphisms is unknown. A neutralizing Ab failed to bind the LIGHT-214K variant, indicating this position as a part of the receptor-binding region. Relative to the predominant reference variant S32/E214, the other variants showed altered avidity with LT beta R and less with HVEM. Heterotrimers of the LIGHT variants decreased binding avidity to DcR3 and minimized the inhibitory effect of DcR3 toward LT beta R-induced activation of NF-kappa B. In patients with immune-mediated inflammatory diseases, such as rheumatoid arthritis, DcR3 protein levels were significantly elevated. Immunohistochemistry revealed synoviocytes as a significant source of DcR3 production, and DcR3 hyperexpression is controlled by posttranscriptional mechanisms. The increased potential for LT beta R signaling, coupled with increased bioavailability due to lower DcR3 avidity, provides a mechanism of how polymorphic variants in LIGHT could contribute to the pathogenesis of inflammatory diseases. ER -Download RIS file
| 00000nam^a2200301^i^4500 | |||
| 001 | 1096147 | ||
| 005 | 20180813140542.0 | ||
| 008 | 110110s2010------------------------eng-- | ||
| 022 | a 0022-1767 | ||
| 024 | a 000280177400073 2 wos | ||
| 024 | a 1854/LU-1096147 2 handle | ||
| 024 | a 10.4049/jimmunol.1001159 2 doi | ||
| 040 | a UGent | ||
| 245 | a Polymorphic variants of LIGHT (TNF superfamily-14) alter receptor avidity and bioavailability | ||
| 260 | c 2010 | ||
| 520 | a The TNF superfamily member homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for herpesvirus entry mediator (HVEM), a receptor expressed by T lymphocytes (LIGHT) [ TNF superfamily (SF)-14], is a key cytokine that activates T cells and dendritic cells and is implicated as a mediator of inflammatory, metabolic, and malignant diseases. LIGHT engages the lymphotoxin-beta receptor (LT beta R) and HVEM (TNFRSF14), but is competitively limited in activating these receptors by soluble decoy receptor-3 (DcR3; TNFRSF6B). Two variants in the human LIGHT alter the protein at E214K (rs344560) in the receptor-binding domain and S32L (rs2291667) in the cytosolic domain; however, the functional impact of these polymorphisms is unknown. A neutralizing Ab failed to bind the LIGHT-214K variant, indicating this position as a part of the receptor-binding region. Relative to the predominant reference variant S32/E214, the other variants showed altered avidity with LT beta R and less with HVEM. Heterotrimers of the LIGHT variants decreased binding avidity to DcR3 and minimized the inhibitory effect of DcR3 toward LT beta R-induced activation of NF-kappa B. In patients with immune-mediated inflammatory diseases, such as rheumatoid arthritis, DcR3 protein levels were significantly elevated. Immunohistochemistry revealed synoviocytes as a significant source of DcR3 production, and DcR3 hyperexpression is controlled by posttranscriptional mechanisms. The increased potential for LT beta R signaling, coupled with increased bioavailability due to lower DcR3 avidity, provides a mechanism of how polymorphic variants in LIGHT could contribute to the pathogenesis of inflammatory diseases. | ||
| 598 | a A1 | ||
| 700 | a Cheung, Timothy C | ||
| 700 | a Coppieters, Ken u GE01 0 001998188882 0 801001660878 9 3225F478-F0EE-11E1-A9DE-61C894A0A6B4 | ||
| 700 | a Sanjo, Hideki | ||
| 700 | a Oborne, Lisa M | ||
| 700 | a Norris, Paula S | ||
| 700 | a Coddington, Amy | ||
| 700 | a Granger, Steven W | ||
| 700 | a Elewaut, Dirk u GE35 u UZGent 0 801000966825 9 F4D38324-F0ED-11E1-A9DE-61C894A0A6B4 | ||
| 700 | a Ware, Carl F | ||
| 650 | a Medicine and Health Sciences | ||
| 653 | a T-CELL-ACTIVATION | ||
| 653 | a LYMPHOTOXIN-BETA-RECEPTOR | ||
| 653 | a HERPESVIRUS ENTRY MEDIATOR | ||
| 653 | a SYSTEMIC-LUPUS-ERYTHEMATOSUS | ||
| 653 | a DECOY RECEPTOR-3 | ||
| 653 | a HEPATOCELLULAR-CARCINOMA | ||
| 653 | a RHEUMATOID-ARTHRITIS | ||
| 653 | a EXPRESSION | ||
| 653 | a LYMPHOCYTE-ACTIVATION | ||
| 653 | a APOPTOSIS | ||
| 773 | t JOURNAL OF IMMUNOLOGY g J. Immunol. 2010. 185 (3) p.1949-1958 q 185:3<1949 | ||
| 856 | 3 Full Text u https://biblio.ugent.be/publication/1096147/file/1096160 z [ugent] y Cheung_2010_JI_185_3_1949.pdf | ||
| 920 | a article | ||
| Z30 | x GE 1 GE01 | ||
| 922 | a UGENT-GE | ||
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