title: IL-1β inhibits ILC3 while favoring NK-cell maturation of umbilical cord blood CD34(+) precursors.
abstract: 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.
authors.affiliation: Dipartimento Medicina Sperimentale (DIMES), Università degli Studi di Genova, Genova, Italy.|UO Immunologia, Azienda Ospedaliera Universitaria San Martino-Istituto Nazionale per la Ricerca sul Cancro (AOUSM-IST), Genova, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ambrosini
authors.affiliation: UO Immunologia, Azienda Ospedaliera Universitaria San Martino-Istituto Nazionale per la Ricerca sul Cancro (AOUSM-IST), Genova, Italy.|Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Loiacono
authors.affiliation: UO Immunologia, Azienda Ospedaliera Universitaria San Martino-Istituto Nazionale per la Ricerca sul Cancro (AOUSM-IST), Genova, Italy.
authors.forename: Romana
authors.initials: R
authors.lastname: Conte
authors.affiliation: Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.affiliation: Dipartimento Medicina Sperimentale (DIMES), Università degli Studi di Genova, Genova, Italy.|UO Immunologia, Azienda Ospedaliera Universitaria San Martino-Istituto Nazionale per la Ricerca sul Cancro (AOUSM-IST), Genova, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Vitale
authors.affiliation: Dipartimento Medicina Sperimentale (DIMES), Università degli Studi di Genova, Genova, Italy.|UO Immunologia, Azienda Ospedaliera Universitaria San Martino-Istituto Nazionale per la Ricerca sul Cancro (AOUSM-IST), Genova, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Mingari
mesh_terms: D018952:Antigens, CD34 / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002469:Cell Separation; D005312:Fetal Blood / Q000276:immunology; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018952:Antigens, CD34; D053583:Interleukin-1beta
keywords: IL-1β; ILC3; Innate immunity; NK cells; NK-cell development