Batf3 maintains autoactivation of Irf8 for commitment of a CD8α+ conventional DC clonogenic progenitor

被引：295

作者：

Grajales-Reyes, Gary E. ^{[1
]}

Iwata, Arifumi ^{[1
]}

Albring, Joern ^{[2
]}

Wu, Xiaodi ^{[1
]}

Tussiwand, Roxane ^{[1
,3
]}

Wumesh, K. C. ^{[1
]}

Kretzer, Nicole M. ^{[1
]}

Briseno, Carlos G. ^{[1
]}

Durai, Vivek ^{[1
]}

Bagadia, Prachi ^{[1
]}

Haldar, Malay ^{[1
]}

Schoenheit, Joerg ^{[4
]}

Rosenbauer, Frank ^{[5
]}

Murphy, Theresa L. ^{[1
]}

Murphy, Kenneth M. ^{[1
,6
]}

机构：

[1] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA

[2] Univ Munster, Dept Med Hematol & Oncol A, D-48149 Munster, Germany

[3] Univ Basel, Dept Biomed, Basel, Switzerland

[4] Helmholtz Assoc, Max Delbruck Ctr Mol Med, Berlin, Germany

[5] Univ Munster, Inst Mol Tumor Biol, D-48149 Munster, Germany

[6] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA

来源：

NATURE IMMUNOLOGY | 2015年 / 16卷 / 07期

基金：

美国国家卫生研究院;

关键词：

DENDRITIC CELL-DEVELOPMENT; TRANSCRIPTION FACTORS; SUPER-ENHANCERS; BONE-MARROW; IN-VIVO; REGULATORY FACTOR-4; SUBSET DEVELOPMENT; STEM-CELLS; T-CELLS; EXPRESSION;

D O I：

10.1038/ni.3197

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

The transcription factors Batf3 and IRF8 are required for the development of CD8 alpha(+) conventional dendritic cells (cDCs), but the basis for their actions has remained unclear. Here we identified two progenitor cells positive for the transcription factor Zbtb46 that separately generated CD8 alpha(+) cDCs and CD4(+) cDCs and arose directly from the common DC progenitor (CDP). Irf8 expression in CDPs required prior autoactivation of Irf8 that was dependent on the transcription factor PU. 1. Specification of the clonogenic progenitor of CD8 alpha(+) cDCs (the pre-CD8 DC) required IRF8 but not Batf3. However, after specification of pre-CD8 DCs, autoactivation of Irf8 became Batf3 dependent at a CD8 alpha(+) cDC-specific enhancer with multiple transcription factor AP1-IRF composite elements (AICEs) within the Irf8 superenhancer. CDPs from Batf3(-/-) mice that were specified toward development into pre-CD8 DCs failed to complete their development into CD8 alpha(+) cDCs due to decay of Irf8 autoactivation and diverted to the CD4(+) cDC lineage.

引用

页码：708 / +

页数：12

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