Interferons modulate Fc is an element of RI-dependent production of autoregulatory IL-10 by circulating human monocytoid dendritic cells

Background: Immature human blood monocytoid dendritic cells (mDCs) express high-affinity receptors for IgE (Fc is an element of RI), yet their exact function and regulation remain poorly understood. Objective: We sought to characterize Fc is an element of RI-dependent cytokine responses and their regulation in circulating human blood mDCs. Methods: Fc is an element of RI-dependent cytokine responses of circulating mDCs were studied by using anti-Fc is an element of RI alpha stimulation. Plasmacytoid dendritic cell (pDC) cross-regulation through Toll-like receptor 9 on these responses was investigated by examining the effects of exogenous IFN-alpha pretreatment and by coculturing pDCs and mDCs stimulated with CpG. Culture supernatants were analyzed by means of ELISA to determine cytokine levels. Cell markers were determined by means of flow cytometry. Results: mDCs express marked levels of Fc is an element of RI (net mean fluorescence intensity, 196 +/- 49; n = 4). After Fc is an element of RT-dependent activation in mDCs, TNF-alpha (2189 +/- 864 pg/10(6) mDCs, n = 3) levels were upregulated within 4 hours, whereas IL-10 (112 +/- 47 pg/106 mDCs, n = 3) levels were detectable only after 24 hours of incubation. After adding IL-10-neutralizing antibody, TNF-alpha Fc is an element of RI-dependent responses were significantly augmented (3903 197 pg/106 mDCs, P < .01, n = 3). Conversely, recombinant IL-10 dose-dependently inhibited Fc is an element of RI-mediated TNF-alpha responses up to 86% 3% (n = 3, P < .001). Pretreatment of mDCs with IFN-alpha (100 U/mL) enhanced Fc is an element of RI-dependent secretion of IL-10 by 3.2-fold (183 +/- 11 pg/106 mDCs, n = 4) compared with that seen in untreated cells (57 +/- 33 pg/10(6) mDCs, P < .001, n = 4). In pDC/mDC cocultures pretreated with CpG, Fc is an element of RI-dependent IL-10 secretion by mDCs was similarly augmented by 3-fold. Conclusions: Autocrine secretion of IL-10, a critical autoregulator of Fc is an element of RI-dependent proinflammatory responses in mDCs, is cross-regulated by IFN-alpha, a major product of Toll-like receptor 9 responses in pDCs that normally promotes T(H)1 immunity. (J Allergy Clin Immunol 2009;123:217-23.)