Potential role for TL1A, the new TNF-family member and potent costimulator of IFN-gamma, in mucosal inflammation

TNF can potentiate IFN-gamma production by activated T cells and other members of the TNF-superfamily play key roles in this effect. A newly discovered TNF-superfamily cytokine (TL1A) could also be involved in initiating or promoting the Th1 response by enhancing IFN-gamma production. The purpose of...

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Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 112(2004), 1 vom: 16. Juli, Seite 66-77
1. Verfasser: Prehn, John L (VerfasserIn)
Weitere Verfasser: Mehdizadeh, Shahab, Landers, Carol J, Luo, Xia, Cha, Stephanie C, Wei, Ping, Targan, Stephan R
Format: Aufsatz
Sprache:English
Veröffentlicht: 2004
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, U.S. Gov't, P.H.S. Receptors, Tumor Necrosis Factor Receptors, Tumor Necrosis Factor, Member 25 TNFRSF25 protein, human TNFSF15 protein, human Tumor Necrosis Factor Ligand Superfamily Member 15 Tumor Necrosis Factor-alpha Interleukin-10 130068-27-8 mehr... Interleukin-4 207137-56-2 RNA 63231-63-0
Beschreibung
Zusammenfassung:TNF can potentiate IFN-gamma production by activated T cells and other members of the TNF-superfamily play key roles in this effect. A newly discovered TNF-superfamily cytokine (TL1A) could also be involved in initiating or promoting the Th1 response by enhancing IFN-gamma production. The purpose of this study was to assess the role of recombinant TL1A on IFN-gamma production by cultured PBMC and lamina propria LPMC and to determine whether TL1A expression is altered in inflammatory bowel disease. IFN-gamma, but not IL-4 or IL-10 production by PBMC and LPL, was dose-dependently augmented by TL1A (or by activation of its receptor, death domain receptor 3 [DR3], with specific mAb) independently of, but in synergy with, IL-12 and IL-18. T cell activating stimuli induced expression of TL1A on the cell membrane (mb-TL1A) in a fraction of peripheral blood (PB) T cells. In the intestinal mucosa, a fraction of lamina propria (LP) T cells, especially CD4+ cells, constitutively expressed mb-TL1A, and the fraction increased in mucosal inflammation. A higher fraction of cells also express the TL1A receptor DR3 in ulcerative colitis and Crohn's disease. TL1A transcript was several times more abundant in RNA from mucosal biopsies taken from inflamed Crohn's disease lesions than in those taken from uninvolved areas. Expression of TL1A and its receptor DR3 by lamina propria mononuclear cells (LPMC) could have significant influence on the severity of mucosal inflammation
Beschreibung:Date Completed 19.08.2004
Date Revised 14.11.2007
published: Print
Citation Status MEDLINE
ISSN:1521-7035