Genetically Modified Lactococcus lactis for Delivery of Human Interleukin-10 to Dendritic Cells
Interleukin-10 (IL-10) plays an indispensable role in mucosal tolerance by programming dendritic cells (DCs) to induce suppressor Th-cells. We have tested the modulating effect of L. lactis secreting human IL-10 (L. lactisIL-10) on DC function in vitro. Monocyte-derived DC incubated with L. lactis...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2012-01-01
|
| Series: | Gastroenterology Research and Practice |
| Online Access: | http://dx.doi.org/10.1155/2012/639291 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832552684184403968 |
|---|---|
| author | Inge L. Huibregtse Sebatian A. Zaat Martien L. Kapsenberg Maria A. Sartori da Silva Maikel P. Peppelenbosch Sander J. H. van Deventer Henri Braat |
| author_facet | Inge L. Huibregtse Sebatian A. Zaat Martien L. Kapsenberg Maria A. Sartori da Silva Maikel P. Peppelenbosch Sander J. H. van Deventer Henri Braat |
| author_sort | Inge L. Huibregtse |
| collection | DOAJ |
| description | Interleukin-10 (IL-10) plays an indispensable role in mucosal tolerance by programming dendritic cells (DCs) to induce suppressor Th-cells. We have tested the modulating effect of L. lactis secreting human IL-10 (L. lactisIL-10) on DC function in vitro. Monocyte-derived DC incubated with L. lactisIL-10 induced effector Th-cells that markedly suppressed the proliferation of allogenic Th-cells as compared to L. lactis. This suppressive effect was only seen when DC showed increased CD83 and CD86 expression. Furthermore, enhanced production of IL-10 was measured in both L. lactisIL-10-derived DC and Th-cells compared to L. lactis-derived DC and Th-cells. Neutralizing IL-10 during DC-Th-cell interaction and coculturing L. lactisIL-10-derived suppressor Th-cells with allogenic Th-cells in a transwell system prevented the induction of suppressor Th-cells. Only 130 pg/mL of bacterial-derived IL-10 and 40 times more exogenously added recombinant human IL-10 were needed during DC priming for the generation of suppressor Th-cells. The spatially restricted delivery of IL-10 by food-grade bacteria is a promising strategy to induce suppressor Th-cells in vivo and to treat inflammatory diseases. |
| format | Article |
| id | doaj-art-0a85c1f2b39044b485d5fbd7923d9723 |
| institution | Kabale University |
| issn | 1687-6121 1687-630X |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Gastroenterology Research and Practice |
| spelling | doaj-art-0a85c1f2b39044b485d5fbd7923d97232025-02-03T05:58:05ZengWileyGastroenterology Research and Practice1687-61211687-630X2012-01-01201210.1155/2012/639291639291Genetically Modified Lactococcus lactis for Delivery of Human Interleukin-10 to Dendritic CellsInge L. Huibregtse0Sebatian A. Zaat1Martien L. Kapsenberg2Maria A. Sartori da Silva3Maikel P. Peppelenbosch4Sander J. H. van Deventer5Henri Braat6Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, The NetherlandsDepartment of Medical Microbiology, Academic Medical Center, 1105 AZ Amsterdam, The NetherlandsDepartment of Cell Biology, Histology, and Dermatology, Academic Medical Center, 1105 AZ Amsterdam, The NetherlandsDepartment of Gastroenterology and Hepatology, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The NetherlandsDepartment of Gastroenterology and Hepatology, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The NetherlandsDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Gastroenterology and Hepatology, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The NetherlandsInterleukin-10 (IL-10) plays an indispensable role in mucosal tolerance by programming dendritic cells (DCs) to induce suppressor Th-cells. We have tested the modulating effect of L. lactis secreting human IL-10 (L. lactisIL-10) on DC function in vitro. Monocyte-derived DC incubated with L. lactisIL-10 induced effector Th-cells that markedly suppressed the proliferation of allogenic Th-cells as compared to L. lactis. This suppressive effect was only seen when DC showed increased CD83 and CD86 expression. Furthermore, enhanced production of IL-10 was measured in both L. lactisIL-10-derived DC and Th-cells compared to L. lactis-derived DC and Th-cells. Neutralizing IL-10 during DC-Th-cell interaction and coculturing L. lactisIL-10-derived suppressor Th-cells with allogenic Th-cells in a transwell system prevented the induction of suppressor Th-cells. Only 130 pg/mL of bacterial-derived IL-10 and 40 times more exogenously added recombinant human IL-10 were needed during DC priming for the generation of suppressor Th-cells. The spatially restricted delivery of IL-10 by food-grade bacteria is a promising strategy to induce suppressor Th-cells in vivo and to treat inflammatory diseases.http://dx.doi.org/10.1155/2012/639291 |
| spellingShingle | Inge L. Huibregtse Sebatian A. Zaat Martien L. Kapsenberg Maria A. Sartori da Silva Maikel P. Peppelenbosch Sander J. H. van Deventer Henri Braat Genetically Modified Lactococcus lactis for Delivery of Human Interleukin-10 to Dendritic Cells Gastroenterology Research and Practice |
| title | Genetically Modified Lactococcus lactis for Delivery of Human Interleukin-10 to Dendritic Cells |
| title_full | Genetically Modified Lactococcus lactis for Delivery of Human Interleukin-10 to Dendritic Cells |
| title_fullStr | Genetically Modified Lactococcus lactis for Delivery of Human Interleukin-10 to Dendritic Cells |
| title_full_unstemmed | Genetically Modified Lactococcus lactis for Delivery of Human Interleukin-10 to Dendritic Cells |
| title_short | Genetically Modified Lactococcus lactis for Delivery of Human Interleukin-10 to Dendritic Cells |
| title_sort | genetically modified lactococcus lactis for delivery of human interleukin 10 to dendritic cells |
| url | http://dx.doi.org/10.1155/2012/639291 |
| work_keys_str_mv | AT ingelhuibregtse geneticallymodifiedlactococcuslactisfordeliveryofhumaninterleukin10todendriticcells AT sebatianazaat geneticallymodifiedlactococcuslactisfordeliveryofhumaninterleukin10todendriticcells AT martienlkapsenberg geneticallymodifiedlactococcuslactisfordeliveryofhumaninterleukin10todendriticcells AT mariaasartoridasilva geneticallymodifiedlactococcuslactisfordeliveryofhumaninterleukin10todendriticcells AT maikelppeppelenbosch geneticallymodifiedlactococcuslactisfordeliveryofhumaninterleukin10todendriticcells AT sanderjhvandeventer geneticallymodifiedlactococcuslactisfordeliveryofhumaninterleukin10todendriticcells AT henribraat geneticallymodifiedlactococcuslactisfordeliveryofhumaninterleukin10todendriticcells |