Author/Authors :
Babacar Cisse، نويسنده , , Michele L. Caton، نويسنده , , Manfred Lehner and Manfred Schroeder، نويسنده , , Takahiro Maeda، نويسنده , , Stefanie Scheu، نويسنده , , Richard Locksley، نويسنده , , Dan Holmberg، نويسنده , , Christiane Zweier، نويسنده , , Nicolette S. den Hollander، نويسنده , , Sarina G. Kant، نويسنده , , Wolfgang Holter، نويسنده , , Anita Rauch، نويسنده , , Yuan Zhuang، نويسنده , , Boris Reizis، نويسنده ,
Abstract :
Plasmacytoid dendritic cells (PDCs) represent a unique immune cell type specialized in type I interferon (IFN) secretion in response to viral nucleic acids. The molecular control of PDC lineage specification has been poorly understood. We report that basic helix-loop-helix transcription factor (E protein) E2-2/Tcf4 is preferentially expressed in murine and human PDCs. Constitutive or inducible deletion of murine E2-2 blocked the development of PDCs but not of other lineages and abolished IFN response to unmethylated DNA. Moreover, E2-2 haploinsufficiency in mice and in human Pitt-Hopkins syndrome patients was associated with aberrant expression profile and impaired IFN response of the PDC. E2-2 directly activated multiple PDC-enriched genes, including transcription factors involved in PDC development (SpiB, Irf8) and function (Irf7). These results identify E2-2 as a specific transcriptional regulator of the PDC lineage in mice and humans and reveal a key function of E proteins in the innate immune system.
