Systemic IL-12 administration alters hepatic dendritic cell stimulation capabilities.
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 incomple...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3302816?pdf=render |
| _version_ | 1818108970118676480 |
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| author | Tim Chan Timothy C Back Jeffrey J Subleski Jonathan M Weiss John R Ortaldo Robert H Wiltrout |
| author_facet | Tim Chan Timothy C Back Jeffrey J Subleski Jonathan M Weiss John R Ortaldo Robert H Wiltrout |
| author_sort | Tim Chan |
| collection | DOAJ |
| description | 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 IFNγ 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. |
| first_indexed | 2024-12-11T02:23:49Z |
| format | Article |
| id | doaj.art-e623811ed0f747109f1da1c1be3d9aa9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T02:23:49Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e623811ed0f747109f1da1c1be3d9aa92022-12-22T01:23:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0173e3330310.1371/journal.pone.0033303Systemic IL-12 administration alters hepatic dendritic cell stimulation capabilities.Tim ChanTimothy C BackJeffrey J SubleskiJonathan M WeissJohn R OrtaldoRobert H WiltroutThe 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 IFNγ 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.http://europepmc.org/articles/PMC3302816?pdf=render |
| spellingShingle | Tim Chan Timothy C Back Jeffrey J Subleski Jonathan M Weiss John R Ortaldo Robert H Wiltrout Systemic IL-12 administration alters hepatic dendritic cell stimulation capabilities. PLoS ONE |
| title | Systemic IL-12 administration alters hepatic dendritic cell stimulation capabilities. |
| title_full | Systemic IL-12 administration alters hepatic dendritic cell stimulation capabilities. |
| title_fullStr | Systemic IL-12 administration alters hepatic dendritic cell stimulation capabilities. |
| title_full_unstemmed | Systemic IL-12 administration alters hepatic dendritic cell stimulation capabilities. |
| title_short | Systemic IL-12 administration alters hepatic dendritic cell stimulation capabilities. |
| title_sort | systemic il 12 administration alters hepatic dendritic cell stimulation capabilities |
| url | http://europepmc.org/articles/PMC3302816?pdf=render |
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