期刊
JOURNAL OF IMMUNOLOGY
卷 199, 期 8, 页码 2668-2679出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1700287
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资金
- Deutsche Forschungsgemeinschaft [KO2964/3-2, SFB1054/B06, TR128/A06]
- European Research Council [CoG 647215]
- Munich Cluster for Systems Neurology (SyNergy) [EXC 1010]
gamma delta T17 cells are a subset of gamma delta 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 Rag1(-/)-recipient mice of Il23r(gfp/+) (IL-23R reporter) bone marrow selectively lack IL-23R(+) gamma delta T17 cells. Despite their absence in secondary lymphoid tissues during homeostasis, gamma delta 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 beta and IL-23 together are able to promote the development of bona fide gamma delta T17 cells from peripheral CD122-IL-23R(-) gamma delta T cells, whereas CD122(+) gamma delta T cells fail to convert into gamma delta T17 cells and remain stable IFN-gamma producers (gamma delta T1 cells). IL-23 is instrumental in expanding extrathymically generated gamma delta T17 cells. In particular, TCR-V gamma 4(+) chain-expressing CD122-IL-23R(-) gamma delta T cells are induced to express IL-23R and IL-17 outside the thymus during skin inflammation. In contrast, TCR-V gamma 1 + gamma delta T cells largely resist this process because prior TCR engagement in the thymus has initiated their commitment to the gamma delta T1 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 gamma delta T17 cells.
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