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Published online before print February 3, 2006

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(Journal of Leukocyte Biology. 2006;79:797-802.)
© 2006 by Society for Leukocyte Biology

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

Andrea Doni^*, Mosca Michela, Barbara Bottazzi^*, Giuseppe Peri^*, Sonia Valentino^*, Nadia Polentarutti^*, Cecilia Garlanda^* and Alberto Mantovani^*,,1

^* Istituto Clinico Humanitas (ICH), Rozzano, Milan, Italy;
Department of Experimental Medicine and Public Health, University of Camerino, Macerata, Italy; and
Institute of General Pathology, University of Milan, Italy

¹Correspondence: Istituto Clinico Humanitas (ICH), via Manzoni, 56 20089 Rozzano, Milan, Italy. E-mail: alberto.mantovani{at}humanitas.it

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)-1ß and was suppressed by dexamethasone, 1, 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- (IFN-). 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-1ß 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 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- 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.

Key Words: pentraxins • cytokines • tissue remodeling

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