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* Laboratory of Immunology, Institute of Hematologic Research,
Laboratory of Pathology, Institute of Oncology Studies, and
Laboratory of Oncology, Institute of Experimental Medicine, Academia Nacional de Medicina, Buenos Aires, Argentina;
Section of Rheumatology, Hospital Rivadavia, Buenos Aires, Argentina;
¶ Department of Biomedical Sciences and Biotechnology, Section of General Pathology and Immunology, University of Brescia, Brescia, Italy; and
|| Istituto Clinico Humanitas, Rozzano, Milan, Italy
The interaction between immune complexes (IC) and the receptors for the Fc portion of IgG (Fc
Rs) triggers regulatory and effector functions in the immune system. In this study, we investigated the effects of IC on differentiation, maturation, and functions of human monocyte-derived dendritic cells (DC). When IC were added on day 0, DC generated on day 6 (IC-DC) showed lower levels of CD1a and increased expression of CD14, MHC class II, and the macrophage marker CD68, as compared with normally differentiated DC. The use of specific blocking FcR mAbs indicated that the effect of IC was exerted mainly through their interaction with FcRI and to a lesser extend with FcRII. Immature IC-DC also expressed higher levels of CD83, CD86, and CD40 and the expression of these maturation markers was not further regulated by LPS. The apparent lack of maturation following TLR stimulation was associated with a decreased production of IL-12, normal secretion of IL-10 and CCL22, and increased production of CXCL8 and CCL2. IC-DC displayed low endocytic activity and a reduced ability to induce allogeneic T cell proliferation both at basal and LPS-stimulated conditions. Altogether, these data reveal that IC strongly affect DC differentiation and maturation. Skewing of DC function from Ag presentation to a proinflammatory phenotype by IC resembles the state of activation observed in DC obtained from patients with chronic inflammatory autoimmune disorders, such as systemic lupus erythematosus disease and arthritis. Therefore, the altered maturation of DC induced by IC may be involved in the pathogenesis of autoimmune diseases.
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 grants from Fundación Antorchas, Buenos Aires, Argentina and Consejo Nacional de Investigaciones Científicas y Técnicas (PIP 6117), Buenos Aires, Argentina (to M.V.); from the Agencia Nacional de Promoción Científica y Tecnológica (SeCyT), Buenos Aires, Argentina (to M.A.I.); and from Ministero dell’Università e della Ricerca Scientifica (to S.S.).
2 Address correspondence and reprint requests to Dr. Marisa Vulcano, Istituto Clinico Humanitas, Viale Manzoni 56, 20089, Rozzano, Milan, Italy. E-mail address: marisavulcano{at}yahoo.com
3 Abbreviations used in this paper: IC, immune complex; SLE, systemic lupus erythematosus; DC, dendritic cell; aggIgG, heat-aggregated IgG; MHCII, MHC class II; mono-DC, monocyte-derived DC.
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