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

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

The transcription factors Batf3 and IRF8 are required for development of CD8α+ conventional dendritic cells (cDCs), but the basis for their actions was unclear. Here, we identify two novel Zbtb46+ progenitors that separately generate CD8α+ and CD4+ cDCs and arise directly from the common DC progenit...

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Bibliographic Details
Main Authors: Grajales-Reyes, Gary E., Iwata, Arifumi, Albring, Jörn, Wu, Xiaodi, Tussiwand, Roxane, Wumesh, KC, Kretzer, Nicole M., Briseño, Carlos G., Durai, Vivek, Bagadia, Prachi, Haldar, Malay, Schönheit, Jörg, Rosenbauer, Frank, Murphy, Theresa L., Murphy, Kenneth M.
Format: Online
Language:English
Published: 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4507574/
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Summary:The transcription factors Batf3 and IRF8 are required for development of CD8α+ conventional dendritic cells (cDCs), but the basis for their actions was unclear. Here, we identify two novel Zbtb46+ progenitors that separately generate CD8α+ and CD4+ cDCs and arise directly from the common DC progenitor (CDP). Irf8 expression in the CDP depends on prior PU.1-dependent autoactivation, and specification of pre-CD8 DC progenitors requires IRF8 but not Batf3. However, upon pre-CD8 DC specification, Irf8 autoactivation becomes Batf3-dependent at a CD8α+ cDC-specific enhancer containing multiple AP1-IRF composite elements (AICEs) within the Irf8 superenhancer. CDPs from Batf3−/− mice that specify toward pre-CD8 DCs fail to complete CD8α+ cDC development due to decay of Irf8 autoactivation, and divert to the CD4+ cDC lineage.

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