| First Author | Chan T | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 3 | Pages | e33303 |
| PubMed ID | 22428016 | Mgi Jnum | J:186913 |
| Mgi Id | MGI:5433776 | Doi | 10.1371/journal.pone.0033303 |
| Citation | Chan T, et al. (2012) Systemic IL-12 administration alters hepatic dendritic cell stimulation capabilities. PLoS One 7(3):e33303 |
| abstractText | The liver is an immunologically unique organ containing tolerogenic dendritic cells (DC) that maintain an immunosuppressive microenvironment. Although systemic IL-12 administration can improve responses to tumors, the effects of IL-12-based treatments on DC, in particular hepatic DC, remain incompletely understood. In this study, we demonstrate systemic IL-12 administration induces a 2-3 fold increase in conventional, but not plasmacytoid, DC subsets in the liver. Following IL-12 administration, hepatic DC became more phenotypically and functionally mature, resembling the function of splenic DC, but differed as compared to their splenic counterparts in the production of IL-12 following co-stimulation with toll-like receptor (TLR) agonists. Hepatic DCs from IL-12 treated mice acquired enhanced T cell proliferative capabilities similar to levels observed using splenic DCs. Furthermore, IL-12 administration preferentially increased hepatic T cell activation and IFNgamma expression in the RENCA mouse model of renal cell carcinoma. Collectively, the data shows systemic IL-12 administration enables hepatic DCs to overcome at least some aspects of the inherently suppressive milieu of the hepatic environment that could have important implications for the design of IL-12-based immunotherapeutic strategies targeting hepatic malignancies and infections. |
