Genetically Modified Lactococcus lactis for Delivery of Human Interleukin-10 to Dendritic Cells

Abstract EN

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.