| First Author | Bist P | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 8 | Pages | 4375-82 |
| PubMed ID | 24048896 | Mgi Jnum | J:206259 |
| Mgi Id | MGI:5548274 | Doi | 10.4049/jimmunol.1301504 |
| Citation | Bist P, et al. (2013) Annexin-A1 regulates TLR-mediated IFN-beta production through an interaction with TANK-binding kinase 1. J Immunol 191(8):4375-82 |
| abstractText | TLRs play a pivotal role in the recognition of bacteria and viruses. Members of the family recognize specific pathogen sequences to trigger both MyD88 and TRIF-dependent pathways to stimulate a plethora of cells. Aberrant activation of these pathways is known to play a critical role in the development of autoimmunity and cancer. However, how these pathways are entirely regulated is not fully understood. In these studies, we have identified Annexin-A1 (ANXA1) as a novel regulator of TLR-induced IFN-beta and CXCL10 production. We demonstrate that in the absence of ANXA1, mice produce significantly less IFN-beta and CXCL10, and macrophages and plasmacytoid dendritic cells have a deficiency in activation following polyinosinic:polycytidylic acid administration in vivo. Furthermore, a deficiency in activation is observed in macrophages after LPS and polyinosinic:polycytidylic acid in vitro. In keeping with these findings, overexpression of ANXA1 resulted in enhanced IFN-beta and IFN-stimulated responsive element promoter activity, whereas silencing of ANXA1 impaired TLR3- and TLR4-induced IFN-beta and IFN-stimulated responsive element activation. In addition, we show that the C terminus of ANXA1 directly associates with TANK-binding kinase 1 to regulate IFN regulatory factor 3 translocation and phosphorylation. Our findings demonstrate that ANXA1 plays an important role in TLR activation, leading to an augmentation in the type 1 IFN antiviral cytokine response. |
