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

Research output: Contribution to journalArticle

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

Keywords

  • Cytokines
  • Pentraxins
  • Tissue remodeling

ASJC Scopus subject areas

  • Cell Biology

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