Regulation of PTX3, a key component of humoral innate immunity in human dendritic cells: Stimulation by IL-10 and inhibition by IFN-γ

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Abstract

The protopypic long pentraxin 3 (PTX3) is a unique, humoral pattern-recognition receptor, which plays a nonredundant function in innate resistance to pathogens. Dendritic cells (DC) of myelomonocytic origin, but not plasmacytoid DC, are a major source of PTX3 in response to Toll-like receptor (TLR) engagment. The present study was designed to explore the regulation of PTX3 production in DC. PTX3 production was induced by TLR ligands, CD40 ligand, and interleukin (IL)-1β and was suppressed by dexamethasone, 1α, 25-dihydroxivitamin D3, and prostaglandin E2. It was unexpected that lipopolysaccharide (LPS)-stimulated PTX3 production was enhanced by IL-10 and inhibited by IL-4 and interferon-γ (IFN-γ). Enhancement of PTX3 production by IL-10 was also evident when Pam3 Cys-Ser-(Lys)4 .3HCl, a TLR2-TLR1 agonist, polyionisicpolycytidylic acid, a TLR3 agonist, and IL-1β were used as stimuli. The effect of IL-10 was blocked by an anti-IL-10 monoclonal antibody (mAb) or an anti-IL-10 receptor α mAb, which also reduced the LPS-induced production. Thus, production of PTX3 in DC is subjected to a distinct regulatory network, with inhibition by IFN-γ and enhancement by IL-10. The amplification by IL-10 of production of a nonredundant component of fluid-phase innate immunity mirrors the IL-10 stimulatory function on B cells in adaptive immunity. As PTX3 is also an extracellular matrix component, IL-10-enhanced PTX3 production may play a role in orchestration of tissue remodeling in chronic inflammation.

Original languageEnglish
Pages (from-to)797-802
Number of pages6
JournalJournal of Leukocyte Biology
Volume79
Issue number4
DOIs
Publication statusPublished - Apr 2006

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Humoral Immunity
Innate Immunity
Interleukin-10
Dendritic Cells
Interferons
Toll-Like Receptors
Interleukin-1
Lipopolysaccharides
Interleukin-10 Receptors
Monoclonal Antibodies
Pattern Recognition Receptors
PTX3 protein
CD40 Ligand
Adaptive Immunity
Dinoprostone
Interleukin-4
Dexamethasone
Extracellular Matrix
B-Lymphocytes
Ligands

Keywords

  • Cytokines
  • Pentraxins
  • Tissue remodeling

ASJC Scopus subject areas

  • Cell Biology

Cite this

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title = "Regulation of PTX3, a key component of humoral innate immunity in human dendritic cells: Stimulation by IL-10 and inhibition by IFN-γ",
abstract = "The protopypic long pentraxin 3 (PTX3) is a unique, humoral pattern-recognition receptor, which plays a nonredundant function in innate resistance to pathogens. Dendritic cells (DC) of myelomonocytic origin, but not plasmacytoid DC, are a major source of PTX3 in response to Toll-like receptor (TLR) engagment. The present study was designed to explore the regulation of PTX3 production in DC. PTX3 production was induced by TLR ligands, CD40 ligand, and interleukin (IL)-1β and was suppressed by dexamethasone, 1α, 25-dihydroxivitamin D3, and prostaglandin E2. It was unexpected that lipopolysaccharide (LPS)-stimulated PTX3 production was enhanced by IL-10 and inhibited by IL-4 and interferon-γ (IFN-γ). Enhancement of PTX3 production by IL-10 was also evident when Pam3 Cys-Ser-(Lys)4 .3HCl, a TLR2-TLR1 agonist, polyionisicpolycytidylic acid, a TLR3 agonist, and IL-1β were used as stimuli. The effect of IL-10 was blocked by an anti-IL-10 monoclonal antibody (mAb) or an anti-IL-10 receptor α mAb, which also reduced the LPS-induced production. Thus, production of PTX3 in DC is subjected to a distinct regulatory network, with inhibition by IFN-γ and enhancement by IL-10. The amplification by IL-10 of production of a nonredundant component of fluid-phase innate immunity mirrors the IL-10 stimulatory function on B cells in adaptive immunity. As PTX3 is also an extracellular matrix component, IL-10-enhanced PTX3 production may play a role in orchestration of tissue remodeling in chronic inflammation.",
keywords = "Cytokines, Pentraxins, Tissue remodeling",
author = "Andrea Doni and Mosca Michela and Barbara Bottazzi and Giuseppe Peri and Sonia Valentino and Nadia Polentarutti and Cecilia Garlanda and Alberto Mantovani",
year = "2006",
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language = "English",
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pages = "797--802",
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TY - JOUR

T1 - Regulation of PTX3, a key component of humoral innate immunity in human dendritic cells

T2 - Stimulation by IL-10 and inhibition by IFN-γ

AU - Doni, Andrea

AU - Michela, Mosca

AU - Bottazzi, Barbara

AU - Peri, Giuseppe

AU - Valentino, Sonia

AU - Polentarutti, Nadia

AU - Garlanda, Cecilia

AU - Mantovani, Alberto

PY - 2006/4

Y1 - 2006/4

N2 - The protopypic long pentraxin 3 (PTX3) is a unique, humoral pattern-recognition receptor, which plays a nonredundant function in innate resistance to pathogens. Dendritic cells (DC) of myelomonocytic origin, but not plasmacytoid DC, are a major source of PTX3 in response to Toll-like receptor (TLR) engagment. The present study was designed to explore the regulation of PTX3 production in DC. PTX3 production was induced by TLR ligands, CD40 ligand, and interleukin (IL)-1β and was suppressed by dexamethasone, 1α, 25-dihydroxivitamin D3, and prostaglandin E2. It was unexpected that lipopolysaccharide (LPS)-stimulated PTX3 production was enhanced by IL-10 and inhibited by IL-4 and interferon-γ (IFN-γ). Enhancement of PTX3 production by IL-10 was also evident when Pam3 Cys-Ser-(Lys)4 .3HCl, a TLR2-TLR1 agonist, polyionisicpolycytidylic acid, a TLR3 agonist, and IL-1β were used as stimuli. The effect of IL-10 was blocked by an anti-IL-10 monoclonal antibody (mAb) or an anti-IL-10 receptor α mAb, which also reduced the LPS-induced production. Thus, production of PTX3 in DC is subjected to a distinct regulatory network, with inhibition by IFN-γ and enhancement by IL-10. The amplification by IL-10 of production of a nonredundant component of fluid-phase innate immunity mirrors the IL-10 stimulatory function on B cells in adaptive immunity. As PTX3 is also an extracellular matrix component, IL-10-enhanced PTX3 production may play a role in orchestration of tissue remodeling in chronic inflammation.

AB - The protopypic long pentraxin 3 (PTX3) is a unique, humoral pattern-recognition receptor, which plays a nonredundant function in innate resistance to pathogens. Dendritic cells (DC) of myelomonocytic origin, but not plasmacytoid DC, are a major source of PTX3 in response to Toll-like receptor (TLR) engagment. The present study was designed to explore the regulation of PTX3 production in DC. PTX3 production was induced by TLR ligands, CD40 ligand, and interleukin (IL)-1β and was suppressed by dexamethasone, 1α, 25-dihydroxivitamin D3, and prostaglandin E2. It was unexpected that lipopolysaccharide (LPS)-stimulated PTX3 production was enhanced by IL-10 and inhibited by IL-4 and interferon-γ (IFN-γ). Enhancement of PTX3 production by IL-10 was also evident when Pam3 Cys-Ser-(Lys)4 .3HCl, a TLR2-TLR1 agonist, polyionisicpolycytidylic acid, a TLR3 agonist, and IL-1β were used as stimuli. The effect of IL-10 was blocked by an anti-IL-10 monoclonal antibody (mAb) or an anti-IL-10 receptor α mAb, which also reduced the LPS-induced production. Thus, production of PTX3 in DC is subjected to a distinct regulatory network, with inhibition by IFN-γ and enhancement by IL-10. The amplification by IL-10 of production of a nonredundant component of fluid-phase innate immunity mirrors the IL-10 stimulatory function on B cells in adaptive immunity. As PTX3 is also an extracellular matrix component, IL-10-enhanced PTX3 production may play a role in orchestration of tissue remodeling in chronic inflammation.

KW - Cytokines

KW - Pentraxins

KW - Tissue remodeling

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