Glucocorticoids affect human dendritic cell differentiation and maturation

Lorenzo Piemonti, Paolo Monti, Paola Allavena, Marina Sironi, Laura Soldini, Biagio Eugenio Leone, Carlo Socci, Valerio Di Carlo

Research output: Contribution to journalArticle

Abstract

Because dendritic cells (DC) play a major role in the initiation of T cell-mediated immunity, we studied the effects of glucocorticoids, well- known inhibitors of the immune and inflammatory response, on the differentiation and maturation of human DC. DC were differentiated from human monocytes by culture with GM-CSF and IL-4 for 7 days with and without dexamethasone (Dex). Cells treated with Dex (10-8 M) (Dex-DC) developed a characteristic dendritic morphology; however, membrane phenotype analysis demonstrated that they were not fully differentiated. Dex-DC expressed low levels of CD1a and, unlike untreated cells, high levels of CD14 and CD16. Molecules involved in Ag presentation (CD40, CD86, CD54) were also impaired. In contrast, molecules involved in Ag uptake (mannose receptor, CD32) and cell adhesion (CD11/CD18, CD54) were up-regulated. After exposure to TNF-α or CD40 ligand, Dex-DC expressed lower levels of CD83 and CD86 than untreated cells. Dex-DC showed a higher endocytic activity, a lower APC function, and a lower capacity to secrete cytokines than untreated cells. Overall, these results indicate that DC differentiated in the presence of Dex are at a more immature stage. Moreover, Dex also partially blocked terminal maturation of already differentiated DC. In conclusion, our data suggest that glucocorticoids may act at the very first step of the immune response by modulating DC differentiation, maturation, and function.

Original languageEnglish
Pages (from-to)6473-6481
Number of pages9
JournalJournal of Immunology
Volume162
Issue number11
Publication statusPublished - Jun 1 1999

Fingerprint

Dendritic Cells
Glucocorticoids
Cell Differentiation
Dexamethasone
Interleukin-7
CD40 Ligand
Granulocyte-Macrophage Colony-Stimulating Factor
Cell Adhesion
Cellular Immunity
Interleukin-4
Monocytes
Cytokines
T-Lymphocytes
Phenotype
Membranes

ASJC Scopus subject areas

  • Immunology

Cite this

Glucocorticoids affect human dendritic cell differentiation and maturation. / Piemonti, Lorenzo; Monti, Paolo; Allavena, Paola; Sironi, Marina; Soldini, Laura; Leone, Biagio Eugenio; Socci, Carlo; Di Carlo, Valerio.

In: Journal of Immunology, Vol. 162, No. 11, 01.06.1999, p. 6473-6481.

Research output: Contribution to journalArticle

Piemonti, Lorenzo ; Monti, Paolo ; Allavena, Paola ; Sironi, Marina ; Soldini, Laura ; Leone, Biagio Eugenio ; Socci, Carlo ; Di Carlo, Valerio. / Glucocorticoids affect human dendritic cell differentiation and maturation. In: Journal of Immunology. 1999 ; Vol. 162, No. 11. pp. 6473-6481.
@article{4b502fcbe76446e29562494da0e6f02f,
title = "Glucocorticoids affect human dendritic cell differentiation and maturation",
abstract = "Because dendritic cells (DC) play a major role in the initiation of T cell-mediated immunity, we studied the effects of glucocorticoids, well- known inhibitors of the immune and inflammatory response, on the differentiation and maturation of human DC. DC were differentiated from human monocytes by culture with GM-CSF and IL-4 for 7 days with and without dexamethasone (Dex). Cells treated with Dex (10-8 M) (Dex-DC) developed a characteristic dendritic morphology; however, membrane phenotype analysis demonstrated that they were not fully differentiated. Dex-DC expressed low levels of CD1a and, unlike untreated cells, high levels of CD14 and CD16. Molecules involved in Ag presentation (CD40, CD86, CD54) were also impaired. In contrast, molecules involved in Ag uptake (mannose receptor, CD32) and cell adhesion (CD11/CD18, CD54) were up-regulated. After exposure to TNF-α or CD40 ligand, Dex-DC expressed lower levels of CD83 and CD86 than untreated cells. Dex-DC showed a higher endocytic activity, a lower APC function, and a lower capacity to secrete cytokines than untreated cells. Overall, these results indicate that DC differentiated in the presence of Dex are at a more immature stage. Moreover, Dex also partially blocked terminal maturation of already differentiated DC. In conclusion, our data suggest that glucocorticoids may act at the very first step of the immune response by modulating DC differentiation, maturation, and function.",
author = "Lorenzo Piemonti and Paolo Monti and Paola Allavena and Marina Sironi and Laura Soldini and Leone, {Biagio Eugenio} and Carlo Socci and {Di Carlo}, Valerio",
year = "1999",
month = "6",
day = "1",
language = "English",
volume = "162",
pages = "6473--6481",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "11",

}

TY - JOUR

T1 - Glucocorticoids affect human dendritic cell differentiation and maturation

AU - Piemonti, Lorenzo

AU - Monti, Paolo

AU - Allavena, Paola

AU - Sironi, Marina

AU - Soldini, Laura

AU - Leone, Biagio Eugenio

AU - Socci, Carlo

AU - Di Carlo, Valerio

PY - 1999/6/1

Y1 - 1999/6/1

N2 - Because dendritic cells (DC) play a major role in the initiation of T cell-mediated immunity, we studied the effects of glucocorticoids, well- known inhibitors of the immune and inflammatory response, on the differentiation and maturation of human DC. DC were differentiated from human monocytes by culture with GM-CSF and IL-4 for 7 days with and without dexamethasone (Dex). Cells treated with Dex (10-8 M) (Dex-DC) developed a characteristic dendritic morphology; however, membrane phenotype analysis demonstrated that they were not fully differentiated. Dex-DC expressed low levels of CD1a and, unlike untreated cells, high levels of CD14 and CD16. Molecules involved in Ag presentation (CD40, CD86, CD54) were also impaired. In contrast, molecules involved in Ag uptake (mannose receptor, CD32) and cell adhesion (CD11/CD18, CD54) were up-regulated. After exposure to TNF-α or CD40 ligand, Dex-DC expressed lower levels of CD83 and CD86 than untreated cells. Dex-DC showed a higher endocytic activity, a lower APC function, and a lower capacity to secrete cytokines than untreated cells. Overall, these results indicate that DC differentiated in the presence of Dex are at a more immature stage. Moreover, Dex also partially blocked terminal maturation of already differentiated DC. In conclusion, our data suggest that glucocorticoids may act at the very first step of the immune response by modulating DC differentiation, maturation, and function.

AB - Because dendritic cells (DC) play a major role in the initiation of T cell-mediated immunity, we studied the effects of glucocorticoids, well- known inhibitors of the immune and inflammatory response, on the differentiation and maturation of human DC. DC were differentiated from human monocytes by culture with GM-CSF and IL-4 for 7 days with and without dexamethasone (Dex). Cells treated with Dex (10-8 M) (Dex-DC) developed a characteristic dendritic morphology; however, membrane phenotype analysis demonstrated that they were not fully differentiated. Dex-DC expressed low levels of CD1a and, unlike untreated cells, high levels of CD14 and CD16. Molecules involved in Ag presentation (CD40, CD86, CD54) were also impaired. In contrast, molecules involved in Ag uptake (mannose receptor, CD32) and cell adhesion (CD11/CD18, CD54) were up-regulated. After exposure to TNF-α or CD40 ligand, Dex-DC expressed lower levels of CD83 and CD86 than untreated cells. Dex-DC showed a higher endocytic activity, a lower APC function, and a lower capacity to secrete cytokines than untreated cells. Overall, these results indicate that DC differentiated in the presence of Dex are at a more immature stage. Moreover, Dex also partially blocked terminal maturation of already differentiated DC. In conclusion, our data suggest that glucocorticoids may act at the very first step of the immune response by modulating DC differentiation, maturation, and function.

UR - http://www.scopus.com/inward/record.url?scp=0033152003&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033152003&partnerID=8YFLogxK

M3 - Article

C2 - 10352262

AN - SCOPUS:0033152003

VL - 162

SP - 6473

EP - 6481

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 11

ER -