IL-1β inhibits ILC3 while favoring NK-cell maturation of umbilical cord blood CD34(+) precursors

NK cells are innate lymphocytes characterized by the expression of nuclear factor interleukin 3 regulated (NFIL3 or E4BP4), eomesodermin (EOMES) transcription factors (TFs), and by the ability to exert cytolytic activity and release IFN‐γ. In the haploidentical‐hematopoietic stem cell transplantation (haplo‐HSCT) setting, CD34+ donor derived NK cells play a major role in the control of leukemic relapses. Therefore, it is important to better define cytokines that influence NK‐cell differentiation from CD34+ precursors. We analyzed the effects of IL‐1β on NK‐cell differentiation from umbilical cord blood (UCB) CD34+ cells. While IL‐1β inhibited CD161+CD56+ cell proliferation, an increased expression of LFA‐1, CD94/NKG2A, KIRs, and perforin on CD56+ cells was detected. In addition, within the CD161+CD56+IL‐1RI+LFA‐1− cell fraction (representing group 3 innate lymphoid cells, ILC3‐like cells), a significant increase of EOMES, NKp46, and CD94/NKG2A receptors, cytolytic granules, and IFN‐γ was detected. This increase was paralleled by a decrease of related orphan receptors (RORγt) TF, NKp44 expression, and IL‐22 production. These data suggest that IL‐1β inhibits ILC3‐ while favoring NK‐cell maturation. Since in haplo‐HSCT conditioning regimen, infections or residual leukemia cells may induce IL‐1β production, this may influence the NK/ILC3 development from donor‐derived CD34+ precursors