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• W1567682988 abstract "The transcription factors mediating the development of CD1d-restricted invariant NKT (iNKT) cells remain incompletely described. Here, we show that loss of the AP-1 transcription factor Fra-2 causes a marked increase in the number of both thymic and peripheral iNKT cells, without affecting the development of other T-lineage cells. The defect is cell-autonomous and is evident in the earliest iNKT precursors. We find that iNKT cells expressing the lower affinity TCRVβ8 are proportionally overrepresented in the absence of Fra-2, indicating altered selection of iNKT cells. There is also widespread dysregulation of AP-1-directed gene expression. In the periphery, mature Fra-2-deficient iNKT cells are able to participate in an immune response, but they have an altered response to Ag, showing increased expansion and producing increased amounts of IL-2 and IL-4 compared with their wild-type counterparts. Unusually, naive Fra-2-deficient T cells also rapidly produce IL-2 and IL-4 upon activation. Taken together, these data define Fra-2 as necessary for regulation of normal iNKT cell development and function, and they demonstrate the central role played by the AP-1 family in this lineage." @default.
• W1567682988 created "2016-06-24" @default.
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• W1567682988 date "2009-07-20" @default.
• W1567682988 modified "2023-10-13" @default.
• W1567682988 title "Aberrant Selection and Function of Invariant NKT Cells in the Absence of AP-1 Transcription Factor Fra-2" @default.
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• W1567682988 doi "https://doi.org/10.4049/jimmunol.0803577" @default.
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