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Laboratory of Immunology, Istituto Dermopatico dell’Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy
IL-10 is a critical cytokine that blocks the maturation of
dendritic cells (DCs), but the relevance of autocrine IL-10 on DC
functions has not been investigated. In this study, we found that
immature monocyte-derived DCs released low but sizeable amounts of
IL-10. After stimulation with bacteria, LPS, lipoteichoic acid, or
soluble CD40 ligand, DCs secreted high levels of IL-10. Addition of an
anti-IL-10-neutralizing Ab to immature DCs as well as to soluble
CD40 ligand- or LPS-maturing DCs led to enhanced expression of surface
CD83, CD80, CD86, and MHC molecules and markedly augmented release of
TNF-
and IL-12, but diminished IL-10 mRNA expression. Moreover, DCs
treated with anti-IL-10 Ab showed an increased capacity to activate
allogeneic T cells and primed naive T cells to a more prominent Th1
polarization. DC maturation and IL-10 neutralization were associated
with enhanced accumulation of the IL-10 receptor binding chain
(IL-10R1) mRNA and intracellular IL-10R1 protein. In contrast, surface
IL-10R1 and IL-10 binding activity diminished in mature DCs. These
results indicate that autocrine IL-10 prevents spontaneous maturation
of DCs in vitro, limits LPS- and CD40-mediated maturation, and
increases IL-10 production by DCs. Moreover, IL-10R expression appears
to be regulated by both transcriptional and posttranscriptional
mechanisms. Endogenous IL-10 and IL-10R can be relevant targets for the
manipulation of DC functions.
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X. Chen, K. Doffek, S. L. Sugg, and J. Shilyansky Phosphatidylserine Regulates the Maturation of Human Dendritic Cells J. Immunol., September 1, 2004; 173(5): 2985 - 2994. [Abstract] [Full Text] [PDF]
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S. Fontana, D. Moratto, S. Mangal, M. De Francesco, W. Vermi, S. Ferrari, F. Facchetti, N. Kutukculer, C. Fiorini, M. Duse, et al. Functional defects of dendritic cells in patients with CD40 deficiency Blood, December 1, 2003; 102(12): 4099 - 4106. [Abstract] [Full Text] [PDF]
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