Development of IL-22–producing NK lineage cells from umbilical cord blood hematopoietic stem cells in the absence of secondary lymphoid tissue

Abstract

Human secondary lymphoid tissues (SLTs) contain interleukin-22 (IL-22)-producing cells with an immature NK phenotype. Given their location, these cells are difficult to study. We have generated large numbers of NK22 cells from hematopoietic stem cells. HSC-derived NK22 cells show a CD56(+)CD117(high)CD94(-) phenotype, consistent with stage III NK progenitors. Like freshly isolated SLT stage III cells, HSC-derived NK22 cells express NKp44, CD161, CCR6, IL1 receptor, AHR, and ROR-γτ. IL-1β and IL-23 stimulation results in significant IL-22 but not interferon-γ production. Supernatant from these cells increases CD54 expression on mesenchymal stem cells. Thus, IL-22-producing NK cells can be generated in the absence of SLT. HSC-derived NK22 cells will be valuable in understanding this rare NK subset and create the opportunity for human translational clinical trials.

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

“…Thus, the expression of LFA-1 marks CD161 + CD56 + CD117 − CD7 + NK cells at late stages of differentiation (expression of CD94/NKG2A, and NCR, IFN-γ production and cytolytic granules). On the other hand, the LFA-1 − fraction (CD161 + CD56 + CD117 +/− CD7 − LFA-1 − CD94/NKG2A − ) is heterogeneous and may contain both conventional NK-cell precursors and ILC3-like cells [26][27][28].…”

“…Recently, in vitro models of human NK-cell development from umbilical cord blood (UCB) derived CD34 + cells have shown that either NK-or ILC3-cell differentiation can be obtained [26][27][28]. Thus, the expression of LFA-1 marks CD161 + CD56 + CD117 − CD7 + NK cells at late stages of differentiation (expression of CD94/NKG2A, and NCR, IFN-γ production and cytolytic granules).…”

“…Although different ILC populations are developmentally related, it has not been clearly established at which stage of development they start to differentiate into distinct cell lineages and whether they maintain a certain degree of plasticity [10,11]. Recently, in vitro models of human NK-cell development from umbilical cord blood (UCB) derived CD34 + cells have shown that either NK-or ILC3-cell differentiation can be obtained [26][27][28]. Thus, the expression of LFA-1 marks CD161 + CD56 + CD117 − CD7 + NK cells at late stages of differentiation (expression of CD94/NKG2A, and NCR, IFN-γ production and cytolytic granules).…”

“…Thus, the expression of LFA-1 marks CD161 + CD56 + CD117 − CD7 + NK cells at late stages of differentiation (expression of CD94/NKG2A, and NCR, IFN-γ production and cytolytic granules). On the other hand, the LFA-1 − fraction (CD161 + CD56 + CD117 +/− CD7 − LFA-1 − CD94/NKG2A − ) is heterogeneous and may contain both conventional NK-cell precursors and ILC3-like cells [26][27][28].Studies on NK-cell receptors, function, and development have been exploited in the haploidentical-hematopoietic stem cell transplantation (haplo-HSCT) setting to treat high-risk leukemias. Indeed, NK cells derived from donor CD34 + precursors play a central role for the successful clinical outcome [29][30][31][32][33].…”

Physiological and Pathological Aspects of Human NK Cells

“…This sequential process of cell marker acquisition identifies NK cell precursor intermediates with different functional properties Grzywacz et al, 2006 Tang et al, 2011). The production of CXCL8 could have a role in the modulation of hematopoietic cell lineage commitment.…”