Regulation of PTX3, a key component of humoral innate immunity in human dendritic cells: stimulation by IL-10 and inhibition by IFN-gamma.
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) engagement. 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)-1beta and was suppressed by dexamethasone, 1alpha, 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-gamma (IFN-gamma). 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-1beta 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 alpha 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-gamma 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.
Doni
Andrea
A
Istituto Clinico Humanitas (ICH), via Manzoni, 56 20089 Rozzano, Milan, Italy.
Michela
Mosca
M
Bottazzi
Barbara
B
Peri
Giuseppe
G
Valentino
Sonia
S
Polentarutti
Nadia
N
Garlanda
Cecilia
C
Mantovani
Alberto
A
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000917:Antibody Formation / Q000276:immunology*; D002097:C-Reactive Protein / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology*; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000683:Serum Amyloid P-Component / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology*; D000099153:Pentraxins
D000911:Antibodies, Monoclonal; D002097:C-Reactive Protein; D007371:Interferon-gamma; D016753:Interleukin-10; D015847:Interleukin-4; D008070:Lipopolysaccharides; D000683:Serum Amyloid P-Component; D000099153:Pentraxins