Impairment of dendritic cell functions in patients with adaptor protein-3 complex deficiency

Alberto Prandini, Valentina Salvi, Francesca Colombo, Daniele Moratto, Luisa Lorenzi, William Vermi, Maria Antonia De Francesco, Lucia Dora Notarangelo, Fulvio Porta, Alessandro Plebani, Fabio Facchetti, Silvano Sozzani, Raffaele Badolato

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)3382-6
Number of pages5
JournalBlood
Volume127
Issue number26
DOIs
Publication statusPublished - Jun 30 2016

Fingerprint

Adaptor Protein Complex 3
Dendritic Cells
Lysosome-Associated Membrane Glycoproteins
Monocytes
Piebaldism
Granzymes
Mixed Lymphocyte Culture Test
T-cells
Lymphocytes
Biopsy
Interleukin-3
Human Herpesvirus 1
Interleukin-12
Neutropenia
Viruses
Interleukin-10
Interferons
Siblings
Assays
Cytoplasm

Keywords

  • Adaptor Protein Complex 3
  • Antigens, CD
  • Cell Adhesion Molecules, Neuronal
  • Cytokines
  • Dendritic Cells
  • Female
  • GPI-Linked Proteins
  • Gene Expression Regulation
  • Granzymes
  • Hermanski-Pudlak Syndrome
  • Herpesvirus 1, Human
  • Humans
  • Immunoglobulins
  • Male
  • Membrane Glycoproteins
  • Monocytes
  • T-Lymphocytes
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Prandini, A., Salvi, V., Colombo, F., Moratto, D., Lorenzi, L., Vermi, W., ... Badolato, R. (2016). Impairment of dendritic cell functions in patients with adaptor protein-3 complex deficiency. Blood, 127(26), 3382-6. https://doi.org/10.1182/blood-2015-06-650689

Impairment of dendritic cell functions in patients with adaptor protein-3 complex deficiency. / Prandini, Alberto; Salvi, Valentina; Colombo, Francesca; Moratto, Daniele; Lorenzi, Luisa; Vermi, William; De Francesco, Maria Antonia; Notarangelo, Lucia Dora; Porta, Fulvio; Plebani, Alessandro; Facchetti, Fabio; Sozzani, Silvano; Badolato, Raffaele.

In: Blood, Vol. 127, No. 26, 30.06.2016, p. 3382-6.

Research output: Contribution to journalArticle

Prandini, A, Salvi, V, Colombo, F, Moratto, D, Lorenzi, L, Vermi, W, De Francesco, MA, Notarangelo, LD, Porta, F, Plebani, A, Facchetti, F, Sozzani, S & Badolato, R 2016, 'Impairment of dendritic cell functions in patients with adaptor protein-3 complex deficiency', Blood, vol. 127, no. 26, pp. 3382-6. https://doi.org/10.1182/blood-2015-06-650689
Prandini A, Salvi V, Colombo F, Moratto D, Lorenzi L, Vermi W et al. Impairment of dendritic cell functions in patients with adaptor protein-3 complex deficiency. Blood. 2016 Jun 30;127(26):3382-6. https://doi.org/10.1182/blood-2015-06-650689
Prandini, Alberto ; Salvi, Valentina ; Colombo, Francesca ; Moratto, Daniele ; Lorenzi, Luisa ; Vermi, William ; De Francesco, Maria Antonia ; Notarangelo, Lucia Dora ; Porta, Fulvio ; Plebani, Alessandro ; Facchetti, Fabio ; Sozzani, Silvano ; Badolato, Raffaele. / Impairment of dendritic cell functions in patients with adaptor protein-3 complex deficiency. In: Blood. 2016 ; Vol. 127, No. 26. pp. 3382-6.
@article{b8a0232add144deea8c89174c3a1f8b0,
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.",
keywords = "Adaptor Protein Complex 3, Antigens, CD, Cell Adhesion Molecules, Neuronal, Cytokines, Dendritic Cells, Female, GPI-Linked Proteins, Gene Expression Regulation, Granzymes, Hermanski-Pudlak Syndrome, Herpesvirus 1, Human, Humans, Immunoglobulins, Male, Membrane Glycoproteins, Monocytes, T-Lymphocytes, Journal Article, Research Support, Non-U.S. Gov't",
author = "Alberto Prandini and Valentina Salvi and Francesca Colombo and Daniele Moratto and Luisa Lorenzi and William Vermi and {De Francesco}, {Maria Antonia} and Notarangelo, {Lucia Dora} and Fulvio Porta and Alessandro Plebani and Fabio Facchetti and Silvano Sozzani and Raffaele Badolato",
note = "{\circledC} 2016 by The American Society of Hematology.",
year = "2016",
month = "6",
day = "30",
doi = "10.1182/blood-2015-06-650689",
language = "English",
volume = "127",
pages = "3382--6",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "26",

}

TY - JOUR

T1 - Impairment of dendritic cell functions in patients with adaptor protein-3 complex deficiency

AU - Prandini, Alberto

AU - Salvi, Valentina

AU - Colombo, Francesca

AU - Moratto, Daniele

AU - Lorenzi, Luisa

AU - Vermi, William

AU - De Francesco, Maria Antonia

AU - Notarangelo, Lucia Dora

AU - Porta, Fulvio

AU - Plebani, Alessandro

AU - Facchetti, Fabio

AU - Sozzani, Silvano

AU - Badolato, Raffaele

N1 - © 2016 by The American Society of Hematology.

PY - 2016/6/30

Y1 - 2016/6/30

N2 - 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.

AB - 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.

KW - Adaptor Protein Complex 3

KW - Antigens, CD

KW - Cell Adhesion Molecules, Neuronal

KW - Cytokines

KW - Dendritic Cells

KW - Female

KW - GPI-Linked Proteins

KW - Gene Expression Regulation

KW - Granzymes

KW - Hermanski-Pudlak Syndrome

KW - Herpesvirus 1, Human

KW - Humans

KW - Immunoglobulins

KW - Male

KW - Membrane Glycoproteins

KW - Monocytes

KW - T-Lymphocytes

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1182/blood-2015-06-650689

DO - 10.1182/blood-2015-06-650689

M3 - Article

VL - 127

SP - 3382

EP - 3386

JO - Blood

JF - Blood

SN - 0006-4971

IS - 26

ER -