High intestinal and systemic levels of decoy receptor 3 (DcR3) and its ligand TL1A in active ulcerative colitis

Bamias, Giorgos; Kaltsa, Garyfallia; Siakavellas, Spyros I.; Papaxoinis, Kostis; Zampeli, Evanthia; Michopoulos, Spyros; Zouboulis-Vafiadis, Irene; Ladas, Spiros D.

doi:10.1016/j.clim.2010.07.001

Cited by 74 publications

(53 citation statements)

References 40 publications

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“…Studies in other rheumatic diseases showed the increase of DcR3 in the serum of systemic lupus erythematosus (SLE) and indicated high disease activity [9]. Consistently, elevated levels of DcR3 were also found in systemic sclerosis (SSc), psoriatic skin lesions and inflammatory bowel diseases [10][11][12]. As DcR3 can induce T cell activation [13], herein, we corroborate these findings by hypothesizing that DcR3 might also contribute to the pathogenesis of rheumatic and immune diseases by inducing T cell.…”

Section: Discussionsupporting

confidence: 83%

Serum and synovial fluid levels of tumor necrosis factor-like ligand 1A and decoy receptor 3 in rheumatoid arthritis

et al. 2015

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Section: Discussionsupporting

confidence: 83%

Serum and synovial fluid levels of tumor necrosis factor-like ligand 1A and decoy receptor 3 in rheumatoid arthritis

et al. 2015

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“…The presence of TL1A in diseased tissues, fluids, and sera from patients of chronic colitis and rheumatoid arthritis (RA) corroborates the findings in animal models (2,5,(17)(18)(19). In vivo studies of different animal models have provided direct evidence supporting the role of TL1A in autoimmune diseases.…”

supporting

confidence: 62%

TNF-like Ligand 1A (TL1A) Gene Knockout Leads to Ameliorated Collagen-Induced Arthritis in Mice: Implication of TL1A in Humoral Immune Responses

Wang

Charpentier

et al. 2013

The Journal of Immunology

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TNF-like ligand 1A (TL1A), also known as TNFSF15, is a member of the TNF superfamily. Its known receptor is death receptor 3 (DR3). In humans, TL1A also binds to a secreted TNF family member called decoy receptor 3, which interferes with the interaction between TL1A and DR3. TL1A/DR3 signal has been implicated in several autoimmune diseases in animal models as well as in clinical conditions. We generated TL1A gene knockout (KO) mice to assess its role in collagen-induced arthritis (CIA), a mouse model of human rheumatoid arthritis. The KO mice were fertile and had no visible anomalies. Their lymphoid organ size and cellularity, T and B cell subpopulations, Th cell and regulatory T cell development in vivo and in vitro, and antiviral immune responses were comparable to those of wild-type mice. However, the KO mice presented ameliorated CIA in terms of clinical scores, disease incidence, and pathological scores. The KO mice had reduced titers of pathogenic anti-collagen Abs in the sera. No apparent defect was found in the function of follicular Th cells. We revealed that plasma cells but not B cells expressed high levels of DR3 and were direct targets of TL1A. In the presence of TL1A, they survived better and produced more pathogenic Ab. This study presented novel knowledge about the role of TL1A in humoral immune responses and its mechanism of action in CIA pathogenesis.

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“…Furthermore, transgenic expression of TL1A in mice has been shown to lead to development of chronic intestinal inflammation (20–22). In humans, elevated expression of local and systemic TL1A has been reported in IBD patients (23, 24), and genetic polymorphisms of TNFSF15 , the gene encoding the TL1A protein, modify the risk for developing IBD in both Caucasian and Asian populations (25, 26). …”

Section: Introductionmentioning

confidence: 99%

A Novel Role for TL1A/DR3 in Protection against Intestinal Injury and Infection

Bamias

Arseneau

et al. 2016

The Journal of Immunology

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Tumor necrosis factor (TNF)-like cytokine 1A (TL1A) is expressed on antigen presenting cells and provides co-stimulatory signals to activated lymphocytes that bear its functional receptor, death receptor 3 (DR3). TL1A/DR3 signaling is involved in the pathogenesis of human and experimental inflammatory bowel disease (IBD). In the present study, we investigated the role of this cytokine/receptor pair in acute intestinal injury/repair pathways. We demonstrate that intact DR3 signaling protected mice from acute DSS colitis, as DR3−/− mice showed more severe mucosal inflammation and increased mortality. DR3−/− mice were compromised in their ability to maintain adequate numbers of CD4+CD25+Foxp3+ T regulatory cells (Tregs) in response to acute mucosal damage. This defect in immune regulation led to a non-specific upregulation of effector pro-inflammatory pathways, which was most prominent for the Th17 immunophenotype. TL1A−/− mice were similarly more susceptible to DSS colitis, although without mortality and with delayed kinetics compared to DR3−/− mice, and also displayed significantly reduced numbers of Tregs. Infection of DR3−/− mice with Salmonella typhimurium was associated with defective microbial clearance and elevated bacterial load. Taken together, our findings indicate a novel protective role for the TL1A/DR3 axis in the regulation of mucosal homeostasis during acute intestinal injury/repair, which contrasts with its known pathogenic function during chronic intestinal inflammation.

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High intestinal and systemic levels of decoy receptor 3 (DcR3) and its ligand TL1A in active ulcerative colitis

Cited by 74 publications

References 40 publications

Serum and synovial fluid levels of tumor necrosis factor-like ligand 1A and decoy receptor 3 in rheumatoid arthritis

Serum and synovial fluid levels of tumor necrosis factor-like ligand 1A and decoy receptor 3 in rheumatoid arthritis

TNF-like Ligand 1A (TL1A) Gene Knockout Leads to Ameliorated Collagen-Induced Arthritis in Mice: Implication of TL1A in Humoral Immune Responses

A Novel Role for TL1A/DR3 in Protection against Intestinal Injury and Infection

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