Results: 2

1.
Figure 1

Figure 1. TL1A-DR3 interactions are critical for effector CD4+T cells at the site of inflammation. From: TL1A and DR3, a TNF-family ligand-receptor pair that promotes lymphocyte costimulation, mucosal hyperplasia and autoimmune inflammation.

TL1A is produced by dendritic cells as a type II transmembrane protein (mTL1A) and then cleaved by metalloproteinases to form soluble TL1A (sTL1A). TL1A costimulates T cell activation and production of cytokines in vitro. However, TL1A-DR3 interactions are apparently not required for T cell priming in vivo. Activated T cells also produce mTL1A but the significance of autocrine TL1A is not known. In the inflamed tissue, endothelial cells and Dendritic Cells activated by inflammatory stimuli produce TL1A and provide costimulation for effector and memory T cells entering the tissue, which is required for efficient expansion and cytokine production by these T cells, leading to greater pathogenicity in animal models of disease.

Fran├žoise Meylan, et al. Immunol Rev. ;244(1):10.1111/j.1600-065X.2011.01068.x.
2.
Figure 2

Figure 2. Distinct effects of transient vs. sustained TL1A expression. From: TL1A and DR3, a TNF-family ligand-receptor pair that promotes lymphocyte costimulation, mucosal hyperplasia and autoimmune inflammation.

Transient expression of TL1A is induced in innate immune cells by microbial and endogenous stimuli including Toll-like Receptor (TLR) ligands and Fc-Receptor (FcR) crosslinking. Similar stimuli provoke transient TNF production. TNF feeds back on these cells through TNFR1 to enhance cellular activation and cytokine production. Transiently expressed TL1A costimulates T cells through DR3 to produce the indicated cytokines, which enhance T cell expansion in inflamed tissues and also further activate antigen-presenting cells in the tissue, completing a positive feedback loop. Chronic TL1A expression promotes the production of IL-13 by cells other than a conventional T cells. IL-13 drives the indicated features of small intestinal pathology. TL1A also costimulates T cells, which alters T cell homeostasis and promotes cellular inflammation in the intestinal lamina propria. (DC: dendritic cells, EC: endothelial cells)

Fran├žoise Meylan, et al. Immunol Rev. ;244(1):10.1111/j.1600-065X.2011.01068.x.

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