title: Genetically Modified Lactococcus lactis for Delivery of Human Interleukin-10 to Dendritic Cells.
abstract: 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.  lactis(IL-10)) on DC function in vitro. Monocyte-derived DC incubated with L.  lactis(IL-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.  lactis(IL-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.  lactis(IL-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.
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Inge L
authors.initials: IL
authors.lastname: Huibregtse
authors.forename: Sebatian A
authors.initials: SA
authors.lastname: Zaat
authors.forename: Martien L
authors.initials: ML
authors.lastname: Kapsenberg
authors.forename: Maria A
authors.initials: MA
authors.lastname: Sartori da Silva
authors.forename: Maikel P
authors.initials: MP
authors.lastname: Peppelenbosch
authors.forename: Sander J H
authors.initials: SJ
authors.lastname: van Deventer
authors.forename: Henri
authors.initials: H
authors.lastname: Braat