Background: IL-10 is a pleiotropic cytokine and potent negative regulator of both innate and adaptive immune responses. Consequently, IL-10-deficient (IL-10-/-) mice have enhanced contact hypersensitivity (CHS) to topical hapten. Objective: Although the importance of IL-10 production by (regulatory) T cells and Langerhans cells in regulating CHS has been established by cell type-specific il-10 gene targeting, it remains elusive to what extent IL-10 controls dendritic cell (DC) function in vivo. Methods: To this aim, we generated mice with a DC-specific deletion of the IL-10 receptor (IL-10R). Results: Despite the ability of IL-10 to inhibit DC maturation in vitro, DCs of resting DC-IL10R-/-mice retained their immature phenotype in vivo. In contrast, IL-10R-/-DCs produced increased levels of proinflammatory cytokines and IL-10 after in vitro stimulation. Induction of CHS was indistinguishable from that seen in control mice at 24 hours after hapten challenge but resulted in increased ear swelling at 48 hours and delayed resolution of the inflammatory reaction. Adoptive T-cell transfer experiments revealed that only T-cell reactivation and not sensitization by IL-10R-/-DCs leads to enhanced CHS. Accordingly, the expression of proinflammatory cytokines and IL-10 was augmented in the skin of DC-IL10R-/-mice after hapten challenge. Conclusion: Our data demonstrate that IL-10 signaling in DCs is dispensable during naive T-cell priming but is critical to prevent an exaggerated effector T-cell response in the skin.

Conditional gene targeting, IL-10 receptor signaling, Langerhans cells, dendritic cells, immune regulation, skin
dx.doi.org/10.1016/j.jaci.2011.08.032, hdl.handle.net/1765/30713
Journal of Allergy and Clinical Immunology
Erasmus MC: University Medical Center Rotterdam

Girard-Madoux, M.J.H, Kel, J.M, Reizis, B, & Clausen, B.E. (2012). IL-10 controls dendritic cell-induced T-cell reactivation in the skin to limit contact hypersensitivity. Journal of Allergy and Clinical Immunology, 129(1). doi:10.1016/j.jaci.2011.08.032