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

First Author  Grajales-Reyes GE Year  2015
Journal  Nat Immunol Volume  16
Issue  7 Pages  708-17
PubMed ID  26054719 Mgi Jnum  J:232963
Mgi Id  MGI:5780515 Doi  10.1038/ni.3197
Citation  Grajales-Reyes GE, et al. (2015) Batf3 maintains autoactivation of Irf8 for commitment of a CD8alpha(+) conventional DC clonogenic progenitor. Nat Immunol 16(7):708-17
abstractText  The transcription factors Batf3 and IRF8 are required for the development of CD8alpha(+) 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 CD8alpha(+) 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 CD8alpha(+) 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 CD8alpha(+) 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 CD8alpha(+) cDCs due to decay of Irf8 autoactivation and diverted to the CD4(+) cDC lineage.
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