Details

Autor(en) / Beteiligte

• Cisse, Babacar
• Caton, Michele L.
• Lehner, Manfred
• Maeda, Takahiro
• Scheu, Stefanie
• Locksley, Richard
• Holmberg, Dan
• Zweier, Christiane
• den Hollander, Nicolette S.
• Kant, Sarina G.
• Holter, Wolfgang
• Rauch, Anita
• Zhuang, Yuan
• Reizis, Boris

Titel

Transcription Factor E2-2 Is an Essential and Specific Regulator of Plasmacytoid Dendritic Cell Development

Ist Teil von

• Cell, 2008-10, Vol.135 (1), p.37-48

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2008

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.