Circulating IRF8-expressing CD123+CD127+ lymphoid progenitors: key players in human hematopoiesis.
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Lymphopoiesis is the process in which B and T cells, and innate lymphoid cells (ILCs) develop from hematopoietic progenitors that exhibit early lymphoid priming. The branching points where lymphoid-primed human progenitors are further specified to B/T/ILC differentiation trajectories remain unclear. Here, we discuss the emerging role of interferon regulatory factor (IRF)8 as a key factor to bridge human lymphoid and dendritic cell (DC) differentiation, and the current evidence for the existence of circulating and tissue-resident CD123+CD127+ lymphoid progenitors. We propose a model whereby DC/B/T/ILC lineage programs in circulating CD123+CD127+ lymphoid progenitors are expressed in balance. Upon tissue seeding, the tissue microenvironment tilts this molecular balance towards a specific lineage, thereby determining in vivo lineage fates. Finally, we discuss the translational implication of these lymphoid precursors.
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1471-4981
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Biotechnology and Biological Sciences Research Council (BB/P002293/1)
Wellcome Trust (203151/Z/16/Z)
Wellcome Trust (203151/A/16/Z)
Medical Research Council (MC_PC_17230)