TY - JOUR
T1 - IL-1β inhibits ILC3 while favoring NK-cell maturation of umbilical cord blood CD34+ precursors
AU - Ambrosini, Paolo
AU - Loiacono, Fabrizio
AU - Conte, Romana
AU - Moretta, Lorenzo
AU - Vitale, Chiara
AU - Mingari, Maria Cristina
PY - 2015/7/1
Y1 - 2015/7/1
N2 - 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.
AB - 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.
KW - IL-1β
KW - ILC3
KW - Innate immunity
KW - NK cells
KW - NK-cell development
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U2 - 10.1002/eji.201445326
DO - 10.1002/eji.201445326
M3 - Article
C2 - 25847448
AN - SCOPUS:84935745570
VL - 45
SP - 2061
EP - 2071
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 7
ER -