title: Impairment of dendritic cell functions in patients with adaptor protein-3 complex deficiency.
abstract: Hermansky-Pudlak syndrome type 2 (HPS2) is a primary immunodeficiency due to adaptor protein-3 (AP-3) complex deficiency. HPS2 patients present neutropenia, partial albinism, and impaired lysosomal vesicles formation in hematopoietic cells. Given the role of dendritic cells (DCs) in the immune response, we studied monocyte-derived DCs (moDCs) and plasmacytoid DCs (pDCs) in two HPS2 siblings. Mature HPS2 moDCs showed impaired expression of CD83 and DC-lysosome-associated membrane protein (LAMP), low levels of MIP1-β/CCL4, MIG/CXCL9, and severe defect of interleukin-12 (IL-12) secretion. DCs in lymph-node biopsies from the same patients showed a diffuse cytoplasm reactivity in a large fraction of DC-LAMP(+) cells, instead of the classical dot-like stain. In addition, analysis of pDC-related functions of blood-circulating mononuclear cells revealed reduced interferon-α secretion in response to herpes simplex virus-1 (HSV-1), whereas granzyme-B induction upon IL-3/IL-10 stimulation was normal. Finally, T-cell costimulatory activity, as measured by mixed lymphocyte reaction assay, was lower in patients, suggesting that function and maturation of DCs is abnormal in patients with HPS2.
authors.affiliation: Department of Clinical and Experimental Sciences, Institute of Molecular Medicine "Angelo Nocivelli,"
authors.forename: Alberto
authors.initials: A
authors.lastname: Prandini
authors.affiliation: Department of Molecular and Translational Medicine, Section of Experimental Oncology and Immunology.
authors.forename: Valentina
authors.initials: V
authors.lastname: Salvi
authors.affiliation: Department of Clinical and Experimental Sciences, Institute of Molecular Medicine "Angelo Nocivelli,"
authors.forename: Francesca
authors.initials: F
authors.lastname: Colombo
authors.affiliation: Department of Clinical and Experimental Sciences, Institute of Molecular Medicine "Angelo Nocivelli,"
authors.forename: Daniele
authors.initials: D
authors.lastname: Moratto
authors.affiliation: Department of Molecular and Translational Medicine, Section of Experimental Oncology and Immunology, Section of Pathology, and.
authors.forename: Luisa
authors.initials: L
authors.lastname: Lorenzi
authors.affiliation: Department of Molecular and Translational Medicine, Section of Experimental Oncology and Immunology, Section of Pathology, and.
authors.forename: William
authors.initials: W
authors.lastname: Vermi
authors.affiliation: Institute of Microbiology, University of Brescia, Brescia, Italy;
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: De Francesco
authors.affiliation: U.O. Oncoematologia Pediatrica e Trapianto di Midollo Osseo c/o Spedali Civili, Brescia, Italy; and.
authors.forename: Lucia Dora
authors.initials: LD
authors.lastname: Notarangelo
authors.affiliation: U.O. Oncoematologia Pediatrica e Trapianto di Midollo Osseo c/o Spedali Civili, Brescia, Italy; and.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Porta
authors.affiliation: Department of Clinical and Experimental Sciences, Institute of Molecular Medicine "Angelo Nocivelli,"
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.affiliation: Department of Molecular and Translational Medicine, Section of Experimental Oncology and Immunology.
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchetti
authors.affiliation: Department of Molecular and Translational Medicine, Section of Experimental Oncology and Immunology, Humanitas Clinical and Research Center, Rozzano, Italy.
authors.forename: Silvano
authors.initials: S
authors.lastname: Sozzani
authors.affiliation: Department of Clinical and Experimental Sciences, Institute of Molecular Medicine "Angelo Nocivelli,"
authors.forename: Raffaele
authors.initials: R
authors.lastname: Badolato
mesh_terms: D033963:Adaptor Protein Complex 3 / Q000172:deficiency* / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D053804:Granzymes / Q000235:genetics / Q000276:immunology; D022861:Hermanski-Pudlak Syndrome / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018259:Herpesvirus 1, Human / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D000097802:CD83 Antigen
chemical_list: D033963:Adaptor Protein Complex 3; D015703:Antigens, CD; D015816:Cell Adhesion Molecules, Neuronal; D016207:Cytokines; D058851:GPI-Linked Proteins; D053804:Granzymes; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen; C095362:limbic system-associated membrane protein; C509213:GZMB protein, human