Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development

被引：563

作者：

Cisse, Babacar ^{[1
]}

Caton, Michele L. ^{[1
]}

Lehner, Manfred ^{[2
]}

Maeda, Takahiro ^{[3
]}

Scheu, Stefanie ^{[4
,5
,6
]}

Locksley, Richard ^{[4
]}

Holmberg, Dan ^{[7
]}

Zweier, Christiane ^{[8
]}

den Hollander, Nicolette S. ^{[9
]}

Kant, Sarina G. ^{[9
]}

Holter, Wolfgang ^{[2
]}

Rauch, Anita ^{[8
]}

Zhuang, Yuan ^{[10
]}

Reizis, Boris ^{[1
]}

机构：

[1] Columbia Univ, Med Ctr, Dept Microbiol, New York, NY 10032 USA

[2] Univ Erlangen Nurnberg, Childrens Univ Hosp, Dept Hematol & Oncol, D-91054 Erlangen, Germany

[3] Nagasaki Univ, Grad Sch Biomed Sci, Nagasaki 8538691, Japan

[4] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Med & Microbiol Immunol, San Francisco, CA 94143 USA

[5] Univ Dusseldorf, Inst Med Microbiol, D-40225 Dusseldorf, Germany

[6] Univ Dusseldorf, Hosp Hyg, D-40225 Dusseldorf, Germany

[7] Umea Univ, Dept Med Biosci, S-90187 Umea, Sweden

[8] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Human Genet, D-91054 Erlangen, Germany

[9] Leiden Univ, Med Ctr, Dept Clin Genet, NL-2300 RC Leiden, Netherlands

[10] Duke Univ, Sch Med, Dept Immunol, Durham, NC 27710 USA

来源：

CELL | 2008年 / 135卷 / 01期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/j.cell.2008.09.016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

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.

引用

页码：37 / 48

页数：12

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