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

Item Type:Article
Title:Batf3 maintains autoactivation of Irf8 for commitment of a CD8α(+) conventional DC clonogenic progenitor
Creators Name:Grajales-Reyes, G.E. and Iwata, A. and Albring, J. and Wu, X. and Tussiwand, R. and Kc, W. and Kretzer, N.M. and Briseno, C.G. and Durai, V. and Bagadia, P. and Haldar, M. and Schoenheit, J. and Rosenbauer, F. and Murphy, T.L. and Murphy, K.M.
Abstract:The transcription factors Batf3 and IRF8 are required for the development of CD8α(+) 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.
Keywords:129 Strain Mice, Base Sequence, Basic-Leucine Zipper Transcription Factors, Bone Marrow Cells, CD8 Antigens, CD24 Antigens, Clone Cells, Cultured Cells, Dendritic Cells, Flow Cytometry, Immunologic Receptors, Interferon Regulatory Factors, Inbred C57BL Mice, Knockout Mice, Molecular Sequence Data, Nucleic Acid Sequence Homology, Oligonucleotide Array Sequence Analysis, Protein Binding, Repressor Proteins, Stem Cells, Transcriptome, Transgenic Mice, Animals, Mice
Source:Nature Immunology
Publisher:Nature Publishing Group
Page Range:708-717
Date:July 2015
Additional Information:Copyright © 2015 Nature America, Inc. All rights reserved.
Official Publication:https://doi.org/10.1038/ni.3197
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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