IL-1β and IL-23 promote extrathymic commitment of CD27⁺CD1222 γδ T cells to γδ T17 cells

gdT17 cells are a subset of gd T cells committed to IL-17 production and are characterized by the expression of IL-23R and CCR6 and lack of CD27 expression. gdT17 cells are believed to arise within a narrow time window during prenatal thymic development. In agreement with this concept, we show in this study that adult Rag12/2 recipient mice of Il23rgfp/+ (IL-23R reporter) bone marrow selectively lack IL-23R+ gdT17 cells. Despite their absence in secondary lymphoid tissues during homeostasis, gdT17 cells emerge in bone marrow chimeric mice upon induction of skin inflammation by topical treatment with imiquimod cream (Aldara). We demonstrate that IL-1β and IL-23 together are able to promote the development of bona fide gdT17 cells from peripheral CD1222IL-23R2 gd T cells, whereas CD122+ gd T cells fail to convert into gdT17 cells and remain stable IFN-g producers (gdT1 cells). IL-23 is instrumental in expanding extrathymically generated gdT17 cells. In particular, TCR-Vg4+ chain-expressing CD1222IL-23R2 gd T cells are induced to express IL-23R and IL-17 outside the thymus during skin inflammation. In contrast, TCR-Vg1+ gd T cells largely resist this process because prior TCR engagement in the thymus has initiated their commitment to the gdT1 lineage. In summary, our data reveal that the peripheral pool of gd T cells retains a considerable degree of plasticity because it harbors ?naive? precursors, which can be induced to produce IL-17 and replenish peripheral niches that are usually occupied by thymus-derived gdT17 cells.