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* Center for Experimental Research and Medical Studies, San Giovanni Battista Hospital, Turin, Italy;
Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy;
Department of Genetics, Biology, and Biochemistry,
Department of Public Health and Microbiology, and
¶ Department of Medicine and Experimental Oncology, University of Turin, Turin, Italy
Dendritic cells (DCs) are indispensable for initiation of primary T cell responses and a hosts defense against infection. Many proinflammatory stimuli induce DCs to mature (mDCs), but little is known about the ability of chemokines to modulate their maturation. In the present study, we report that CCL16 is a potent maturation factor for monocyte-derived DCs (MoDCs) through differential use of its four receptors and an indirect regulator of Th cell differentiation. MoDCs induced to mature by CCL16 are characterized by increased expression of CD80 and CD86, MHC class II molecules, and ex novo expression of CD83 and CCR7. They produce many chemokines to attract monocytes and T cells and are also strong stimulators in activating allogeneic T cells to skew toward Th1 differentiation. Interestingly, they are still able to take up Ag and express chemokine receptors usually bound by inflammatory ligands and can be induced to migrate to different sites where they capture Ags. Our findings indicate that induction of MoDC maturation is an important property of CCL16 and suggest that chemokines may not only organize the migration of MoDCs, but also directly regulate their ability to prime T cell responses.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Italian Association for Cancer Research, the Italian Ministry for Education, the Universities and Research, Fondi incentivazione della Ricerca di Base and Progetti di Ricerca di Interesse Nazionale, and Compagnia San Paolo, Special Project Oncology.
2 Address correspondence and reprint requests to Professor Mirella Giovarelli, Department of Experimental Medicine and Oncology, Corso Raffaello 30, 10125 Torino, Italy. E-mail address: mirella.giovarelli{at}unito.it
3 Abbreviations used in this paper: DC, dendritic cell; CCL16/mDC, MoDC induced to mature in the presence of CCL16; iDC, immature DC; LN, lymph node; mDC, DC induced to mature in the presence of TNF-
plus IL-1
; MFI, mean fluorescence intensity; MoDC, monocyte-derived DC; PLC, phospholipase C; PTX, pertussis toxin.
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