DC activated via dectin-1 convert Treg into IL-17 producers

Th cells producing IL-17 play a pro-inflammatory role at mucosal surfaces. Treg at the same sites dampen inflammation and prevent immunopathology. Th cells producing IL-17 (Th17) and Treg are thought to be distinct populations defined by expression of the transcription factors ROR-γt and Foxp3, respectively. Here, we show that mouse CD25⁺Foxp3⁺ Treg can be converted into a hybrid T-cell population characterized by the expression of Foxp3 and ROR-γt and the production of IL-17. Conversion was observed upon coculture with DC selectively activated via dectin-1, a C-type lectin receptor involved in fungal recognition, and depended on IL-23 produced by DC. Within the Foxp3⁺ population, only Foxp3⁺ROR-γt⁺ T cells but not Foxp3⁺ROR-γt⁻-T cells become Foxp3⁺IL-17⁺ T cells. These results indicate that some Foxp3⁺ T cells can produce IL-17 while retaining Foxp3 expression and suggest that Treg could play an unexpected pro-inflammatory role in some settings.