| First Author | Ivanov S | Year | 2007 |
| Journal | Blood | Volume | 110 |
| Issue | 6 | Pages | 1970-81 |
| PubMed ID | 17548579 | Mgi Jnum | J:146403 |
| Mgi Id | MGI:3837525 | Doi | 10.1182/blood-2006-09-044776 |
| Citation | Ivanov S, et al. (2007) A novel role for HMGB1 in TLR9-mediated inflammatory responses to CpG-DNA. Blood 110(6):1970-81 |
| abstractText | CpG-DNA or its synthetic analog CpG-ODN activates innate immunity through Toll-like receptor 9 (TLR9). However, the mechanism of TLR9 activation by CpG-DNA remains elusive. Here we have identified HMGB1 as a CpG-ODN-binding protein. HMGB1 interacts and preassociates with TLR9 in the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), and hastens TLR9's redistribution to early endosomes in response to CpG-ODN. CpG-ODN stimulates macrophages and dendritic cells to secrete HMGB1; in turn, extracellular HMGB1 accelerates the delivery of CpG-ODNs to its receptor, leading to a TLR9-dependent augmentation of IL-6, IL-12, and TNFalpha secretion. Loss of HMGB1 leads to a defect in the IL-6, IL-12, TNFalpha, and iNOS response to CpG-ODN. However, lack of intracellular TLR9-associated HMGB1 can be compensated by extracellular HMGB1. Thus, the DNA-binding protein HMGB1 shuttles in and out of immune cells and regulates inflammatory responses to CpG-DNA. |
