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- W4313382019 startingPage "202.22" @default.
- W4313382019 abstract "Abstract Dendritic cells (DC) comprise plasmacytoid DC (pDC) and conventional DC (cDC) subsets; the latter is further separated into type 1 (cDC1) and type 2 (cDC2). These cells play a role in initiating and modulating immune responses. Their development is controlled by a network of transcription factors including E proteins consisting of E12, E47, HEB and E2-2, which share a basic helix-loop-helix domain mediating dimerization and DNA binding. Their activity is regulated by their antagonists, Id1-4. The balance between E and Id proteins regulates the transcription of E protein target genes. While E2-2 is essential for pDC differentiation and Id2 is indispensable for cDC1 formation, little is known about how the balance between E and Id proteins controls the early steps of the commitment of common DC precursors (CDP) to the diverse DC subsets. To address this, we used a mouse model that inducibly expresses a chimeric protein, ET2, which contains the DNA binding domain of Tal1 and the transactivation domains of E47. It can compete with Id proteins to bind endogenous E proteins and restore their DNA binding activity, thus increasing net E protein activity. Our data indicated that ET2 expression inhibited the differentiation of pDC and cDC2 subsets in vivo and in vitro. In contrast, cDC1 production was slightly elevated in steady state but dramatically increased in allergic reactions. Furthermore, we detected an augmented proportion of the newly identified cDC1 precursors and decreased representation of cDC2 precursors, suggesting E proteins skew CDPs toward the cDC1 lineage. These results are consistent with reports that E proteins activate IRF8 gene transcription. Further investigation is in progress to elucidate the molecular mechanisms." @default.
- W4313382019 created "2023-01-06" @default.
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- W4313382019 date "2017-05-01" @default.
- W4313382019 modified "2023-09-25" @default.
- W4313382019 title "E protein activity in DC precursors dictates the differentiation outcome of DC subsets." @default.
- W4313382019 doi "https://doi.org/10.4049/jimmunol.198.supp.202.22" @default.
- W4313382019 hasPublicationYear "2017" @default.
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