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Activation of FcRI on Monocytes Triggers Differentiation into Immature Dendritic Cells That Induce Autoreactive T Cell Responses¹

Motoyuki Tanaka^*,, Stephan R. Krutzik^*, Peter A. Sieling^*, Delphine J. Lee^*, Thomas H. Rea and Robert L. Modlin^2,*,

^* Division of Dermatology and Department of Microbiology and Immunology David Geffen School of Medicine, University of California, Los Angeles, CA 90095; and Section of Dermatology, University of Southern California School of Medicine, Los Angeles, CA 90033

The formation of immune complexes results in activation of the innate immune system and subsequent induction of host inflammatory responses. In particular, the binding of IgG immune complexes to FcR on monocytes triggers potent inflammatory responses leading to tissue injury in disease. We investigated whether activation of monocytes via FcR induced cell differentiation, imparting specific inflammatory functions of the innate immune response. Human IgG alone induced monocytes to differentiate into cells with an immature dendritic cell (iDC) phenotype, including up-regulation of CD1b, CD80, CD86, and CD206. Differentiation into CD1b⁺ iDC was dependent on activation via CD64 (FcRI) and induction of GM-CSF. The human IgG-differentiated iDC were phenotypically different from GM-CSF-derived iDC at the same level of CD1b expression, with higher cell surface CD86, but lower MHC class II, CD32, CD206, and CD14. Finally, in comparison to GM-CSF-derived iDC, IgG-differentiated iDC were more efficient in activating T cells in both autologous and allogeneic mixed lymphocyte reactions but less efficient at presenting microbial Ag to T cells. Therefore, activation of FcRI on monocytes triggers differentiation into specialized iDC with the capacity to expand autoreactive T cells that may contribute to the pathogenesis of immune complex-mediated tissue injury.

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 in part by grants from the Heiser Program for Research in Leprosy and Tuberculosis of the New York Community Trust, the Japan Antibiotics Research Association Pfizer Infectious Diseases Fund 2005, and National Institutes of Health Grants AR40312 and A122553.

² Address correspondence and reprint requests to Dr. Robert L. Modlin, University of California, Division of Dermatology, 52-121, HS, 10833 Le Conte Avenue, Los Angeles, CA 90095. E-mail address: rmodlin{at}mednet.ucla.edu

³ Abbreviations used in this paper: DC, dendritic cell; h, human; iDC, immature DC; MFI, mean fluorescence intensity; MHC II, MHC class II; qPCR, quantitative real-time PCR.