Study summary · research use only
The FoxO4/DKK3 axis represses IFN-γ expression by Th1 cells and limits antimicrobial immunity
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this mouse study, researchers examined the role of the transcription factor FoxO4 in T cells. Loss of FoxO4 in T cells increased IFN-γ production by Th1 cells in vitro, and conditional deletion of FoxO4 in CD4+ T cells enhanced T cell responses to Listeria monocytogenes infection in vivo. Genome-wide occupancy and transcriptomic analyses identified Dkk3 as a direct transcriptional target of FoxO4, and recombinant DKK3 protein restored normal IFN-γ production in FoxO4-deficient Th1 cells by lowering Lef1 expression. The authors describe a FoxO4/DKK3 axis in Th1 cell differentiation and suggest it as a possible target of interest for immune-related disease research.
Abstract
Forkhead box O transcriptional factors, especially FoxO1 and FoxO3a, play critical roles in physiologic and pathologic immune responses. However, the function of FoxO4, another main member of the FoxO family, in lymphoid cells is still poorly understood. Here, we showed that loss of FoxO4 in T cells augmented IFN-γ production of Th1 cells in vitro. Correspondingly, conditional deletion of FoxO4 in CD4+ T cells enhanced T cell-specific responses to Listeria monocytogenes infection in vivo. Genome-wide occupancy and transcriptomic analyses identified Dkk3 (encoding the Dickkopf-3 protein) as a direct transcriptional target of FoxO4. Consistent with the FoxO4-DKK3 relationship, recombinant DKK3 protein restored normal levels of IFN-γ production in FoxO4-deficient Th1 cells through the downregulation of lymphoid enhancer-binding factor 1 (Lef1) expression. Together, our data suggest a potential FoxO4/DKK3 axis in Th1 cell differentiation, providing what we believe to be an important insight and supplement for FoxO family proteins in T lymphocyte biology and revealing a promising target for the treatment of immune-related diseases.
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