| First Author | Jia LG | Year | 2016 |
| Journal | J Immunol | Volume | 197 |
| Issue | 1 | Pages | 377-86 |
| PubMed ID | 27233964 | Mgi Jnum | J:309816 |
| Mgi Id | MGI:6709468 | Doi | 10.4049/jimmunol.1502466 |
| Citation | Jia LG, et al. (2016) A Novel Role for TL1A/DR3 in Protection against Intestinal Injury and Infection. J Immunol 197(1):377-86 |
| abstractText | TNF-like cytokine 1A (TL1A) is expressed on APCs and provides costimulatory 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. In the current 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 dextran sodium sulfate colitis because 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(+) regulatory T cells in response to acute mucosal damage. This defect in immune regulation led to a nonspecific upregulation of effector proinflammatory pathways, which was most prominent for the Th17 immunophenotype. TL1A(-/-) mice were similarly more susceptible to dextran sodium sulfate colitis, although without mortality and with delayed kinetics compared with DR3(-/-) mice, and also displayed significantly reduced numbers of regulatory T cells. 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. |
