title: NFKB1 regulates human NK cell maturation and effector functions.
abstract: NFKB1, a component of the canonical NF-κB pathway, was recently reported to be mutated in a limited number of CVID patients. CVID-associated mutations in NFKB2 (non-canonical pathway) have previously been shown to impair NK cell cytotoxic activity. Although a biological function of NFKB1 in non-human NK cells has been reported, the role of NFKB1 mutations for human NK cell biology and disease has not been investigated yet. We decided therefore to evaluate the role of monoallelic NFKB1 mutations in human NK cell maturation and functions. We show that NFKB1 mutated NK cells present impaired maturation, defective cytotoxicity and reduced IFN-γ production upon in vitro stimulation. Furthermore, human IL-2 activated NFKB1 mutated NK cells fail to up-regulate the expression of the activating marker NKp44 and show reduced proliferative capacity. These data suggest that NFKB1 plays an essential novel role for human NK cell maturation and effector functions.
authors.affiliation: Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia, Spedali Civili di Brescia, Italy. Electronic address: vlougarisbs@yahoo.com.
authors.forename: Vassilios
authors.initials: V
authors.lastname: Lougaris
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Patrizi
authors.affiliation: Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia, Spedali Civili di Brescia, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Baronio
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tabellini
authors.affiliation: Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia, Spedali Civili di Brescia, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Tampella
authors.affiliation: Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia, Spedali Civili di Brescia, Italy.
authors.forename: Eufemia
authors.initials: E
authors.lastname: Damiati
authors.affiliation: Center for Chronic Immunodeficiency (CCI), Medical Center, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Natalie
authors.initials: N
authors.lastname: Frede
authors.affiliation: Radboud University Medical Centre, Department of Internal Medicine, Nijmegen 6525, HP, The Netherlands.
authors.forename: Jos W M
authors.initials: JWM
authors.lastname: van der Meer
authors.affiliation: Center for Chronic Immunodeficiency (CCI), Medical Center, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Fliegauf
authors.affiliation: Center for Chronic Immunodeficiency (CCI), Medical Center, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Bodo
authors.initials: B
authors.lastname: Grimbacher
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Parolini
authors.affiliation: Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia, Spedali Civili di Brescia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
mesh_terms: D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D016328:NF-kappa B / Q000276:immunology; D052002:NF-kappa B p50 Subunit / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D007371:Interferon-gamma
keywords: Cytotoxicity; Interferon-γ; NFKB1; Natural killer cells