Disease relevance of Tnfsf15

• Blockade of the TL1A/DR3 pathway may, therefore, offer therapeutic opportunities in Crohn's disease [1].
• Role of TL1A and its receptor DR3 in two models of chronic murine ileitis [1].
• Our results raise the possibility that interaction(s) between TL1A expressed on antigen-presenting cells and tm DR3 on lymphocytes may be of particular importance for the pathogenesis of chronic inflammatory conditions that depend on IFN-gamma secretion, including inflammatory bowel disease [1].
• Expression of the tg TCR complex was selectively downregulated in TL1 cells growing in H-2b+ male SCID recipients [2].
• The thymic lymphoma cell line was cloned and one of the subclones, TL1, was studied [2].

High impact information on Tnfsf15

• Through this interaction, TL1A induces secretion of IFN-gamma and may, therefore, participate in the development of T helper-1-type effector responses [1].
• We also report that TL1A acts preferentially on memory CD4(+)/CD45RB(lo) murine lymphocytes by significantly inducing their proliferation, whereas it does not affect the proliferation of the naïve CD4(+)/CD45RB(hi) T helper cell subpopulation [1].
• In addition, within isolated lamina propria mononuclear cells from mice with inflammation, TL1A is primarily expressed on CD11c(high) dendritic cells [1].
• Decoy receptor 3 (DcR3), a soluble receptor for FasL, LIGHT, and TL1A, induces osteoclast formation from monocyte, macrophage, and bone stromal marrow cells [3].
• These results suggest that TNF-alpha signaling in chondrocytes controls vascularization of cartilage through the regulation of angiopoietin and VEGI factors which play counterbalancing roles in the induction of growth arrest, or apoptosis in endothelial cells [4].

Biological context of Tnfsf15

• To investigate critical sequences in the VEGI promoter, a series of deleted and truncated segments were constructed from a 2300 bp promoter construct (-2201/+96) linked to a luciferase reporter gene [5].
• Using two immunogenetically distinct animal models of Crohn's disease, we demonstrate that induction of intestinal inflammation is associated with significant up-regulation of TL1A and tm DR3 in the inflamed mucosa [1].
• However, the malignant in vivo growth potential of TL1 cells was comparable, irrespectively of the sex and haplotype of the SCID recipient [2].
• In addition, TL1 cell proliferation was inhibited by coculture with male and female H-2b+ cells [2].
• In conclusion, our data show that the growth of TL1 cells in vitro is suppressed by physiological ligation of their TCR complex, whereas TL1 cells, by downregulation of their TCR, may escape TCR-ligation-induced suppression in vivo [2].

Anatomical context of Tnfsf15

• We identified and cloned approx. 2.2 kb of the VEGI promoter from mouse cerebral endothelial cells [5].
• TL1A is a TNF-like cytokine that binds to the death-domain receptor (DR)3 and provides costimulatory signals to activated lymphocytes [1].

Other interactions of Tnfsf15

• These findings suggest that the transcription factor NF-kappaB plays an important role in the regulation of VEGI expression [5].

Analytical, diagnostic and therapeutic context of Tnfsf15

• Following adoptive transfer into both H-2b+ and H-2d+ SCID recipient mice, TL1 cells showed rapid, malignant growth and infiltrated lymphoid and nonlymphoid organs [2].

References