| First Author | Diehl GE | Year | 2004 |
| Journal | Immunity | Volume | 21 |
| Issue | 6 | Pages | 877-89 |
| PubMed ID | 15589175 | Mgi Jnum | J:94681 |
| Mgi Id | MGI:3513694 | Doi | 10.1016/j.immuni.2004.11.008 |
| Citation | Diehl GE, et al. (2004) TRAIL-R as a negative regulator of innate immune cell responses. Immunity 21(6):877-89 |
| abstractText | TRAIL receptor (TRAIL-R) signaling has been implicated in inducing apoptosis in tumor cells, but little is understood about its physiological function. Here, we report the generation and characterization of TRAIL-R(-/-) mice, which develop normal lymphocyte populations but possess enhanced innate immune responses. TRAIL-R(-/-) mice exhibited increased clearance of murine cytomegalovirus that correlated with increased levels of IL-12, IFN-alpha, and IFN-gamma. Stimulation of macrophages with Mycobacterium and Toll-like receptor (TLR)-2, -3, and -4, but not TLR9, ligands resulted in high levels of TRAIL upregulation and enhanced cytokine production in TRAIL-R(-/-) cells. The immediate-early TLR signaling events in TRAIL-R(-/-) macrophages and dendritic cells are normal, but I kappa B-alpha homeostatic regulation and NF-kappa B activity at later time points is perturbed. These data suggest that TRAIL-R negatively regulates innate immune responses. |
