| First Author | Gilbert MR | Year | 2007 |
| Journal | J Immunol | Volume | 178 |
| Issue | 8 | Pages | 4803-10 |
| PubMed ID | 17404261 | Mgi Jnum | J:145201 |
| Mgi Id | MGI:3833812 | Doi | 10.4049/jimmunol.178.8.4803 |
| Citation | Gilbert MR, et al. (2007) Dendritic cells from lupus-prone mice are defective in repressing immunoglobulin secretion. J Immunol 178(8):4803-10 |
| abstractText | Autoimmunity results from a breakdown in tolerance mechanisms that regulate autoreactive lymphocytes. We recently showed that during innate immune responses, secretion of IL-6 by dendritic cells (DCs) maintained autoreactive B cells in an unresponsive state. In this study, we describe that TLR4-activated DCs from lupus-prone mice are defective in repressing autoantibody secretion, coincident with diminished IL-6 secretion. Reduced secretion of IL-6 by MRL/lpr DCs reflected diminished synthesis and failure to sustain IL-6 mRNA production. This occurred coincident with lack of NF-kappaB and AP-1 DNA binding and failure to sustain IkappaBalpha phosphorylation. Analysis of individual mice showed that some animals partially repressed Ig secretion despite reduced levels of IL-6. This suggests that in addition to IL-6, DCs secrete other soluble factor(s) that regulate autoreactive B cells. Collectively, the data show that MRL/lpr mice are defective in DC/IL-6-mediated tolerance, but that some individuals maintain the ability to repress autoantibody secretion by an alternative mechanism. |
