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

Authors :
Grajales-Reyes, Gary E
Iwata, Arifumi
Albring, Jörn
Wu, Xiaodi
Tussiwand, Roxane
KC, Wumesh
Kretzer, Nicole M
Briseño, Carlos G
Durai, Vivek
Bagadia, Prachi
Haldar, Malay
Schönheit, Jörg
Rosenbauer, Frank
Murphy, Theresa L
Murphy, Kenneth M
Source :
Nature Immunology; Jul2015, Vol. 16 Issue 7, p708-717, 10p, 8 Graphs
Publication Year :
2015

Abstract

The transcription factors Batf3 and IRF8 are required for the development of CD8α<superscript>+</superscript> 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 CD8α<superscript>+</superscript> cDCs and CD4<superscript>+</superscript> 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 CD8α<superscript>+</superscript> 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 CD8α<superscript>+</superscript> cDC-specific enhancer with multiple transcription factor AP1-IRF composite elements (AICEs) within the Irf8 superenhancer. CDPs from Batf3<superscript>−/−</superscript> mice that were specified toward development into pre-CD8 DCs failed to complete their development into CD8α<superscript>+</superscript> cDCs due to decay of Irf8 autoactivation and diverted to the CD4<superscript>+</superscript> cDC lineage. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
15292908
Volume :
16
Issue :
7
Database :
Complementary Index
Journal :
Nature Immunology
Publication Type :
Academic Journal
Accession number :
103302456
Full Text :
https://doi.org/10.1038/ni.3197