Circulating IRF8-expressing CD123+CD127+ lymphoid progenitors: key players in human hematopoiesis

Trends Immunol. 2023 Sep;44(9):678-692. doi: 10.1016/j.it.2023.07.004. Epub 2023 Aug 15.

Abstract

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.

Keywords: IRF8; hematopoiesis; hematopoietic tissues; human; lineage cell fate; lymphoid progenitor cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Hematopoiesis
  • Humans
  • Immunity, Innate*
  • Interferon Regulatory Factors
  • Interleukin-3 Receptor alpha Subunit*
  • Lymphocytes

Substances

  • Interferon Regulatory Factors
  • Interleukin-3 Receptor alpha Subunit
  • interferon regulatory factor-8