IL-1? and IL-23 Promote Extrathymic Commitment of CD27+CD122- ?? T Cells to ??T17 Cells.

??T17 cells are a subset of ?? T cells committed to IL-17 production and are characterized by the expression of IL-23R and CCR6 and lack of CD27 expression. ??T17 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 Rag1-/- recipient mice of Il23rgfp/+ (IL-23R reporter) bone marrow selectively lack IL-23R+ ??T17 cells. Despite their absence in secondary lymphoid tissues during homeostasis, ??T17 cells emerge in bone marrow chimeric mice upon induction of skin inflammation by topical treatment with imiquimod cream (Aldara). We demonstrate that IL-1? and IL-23 together are able to promote the development of bona fide ??T17 cells from peripheral CD122-IL-23R- ?? T cells, whereas CD122+ ?? T cells fail to convert into ??T17 cells and remain stable IFN-? producers (??T1 cells). IL-23 is instrumental in expanding extrathymically generated ??T17 cells. In particular, TCR-V?4+ chain-expressing CD122-IL-23R- ?? T cells are induced to express IL-23R and IL-17 outside the thymus during skin inflammation. In contrast, TCR-V?1+ ?? T cells largely resist this process because prior TCR engagement in the thymus has initiated their commitment to the ??T1 lineage. In summary, our data reveal that the peripheral pool of ?? 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 ??T17 cells.     «

??T17 cells are a subset of ?? T cells committed to IL-17 production and are characterized by the expression of IL-23R and CCR6 and lack of CD27 expression. ??T17 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 Rag1-/- recipient mice of Il23rgfp/+ (IL-23R reporter) bone marrow selectively lack IL-23R+ ??T17 cells. Despite their absence in secondary lymphoid tissues during homeostasis, ??T...     »