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

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 Pam3Cys‐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.