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Dendritic Cell Differentiation Signals Induce Anti-Inflammatory Properties in Human Adult Microglia¹

Caroline Lambert^*,, Julie Desbarats^*, Nathalie Arbour, Jeffery A. Hall, Andre Olivier, Amit Bar-Or and Jack P. Antel^2,

^* Physiology Department and Neuroimmunology Unit, Montreal Neurology Institute, McGill University, Montréal, Québec, Canada; Research Center of the Centre Hospitalier de l’Université de Montréal-Notre-Dame Hospital, University of Montreal, Montréal, Québec, Canada; and Department of Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, Québec, Canada

Microglia are resident cells of the CNS that belong to the myeloid cell lineage. In experimental models of neuroinflammation, they have limited capacity to function as APCs when compared with dendritic cells (DCs). Human peripheral blood monocytes have the plasticity to differentiate into mature DCs when exposed to GM-CSF and IL-4 followed by LPS. In this study we addressed the potential of human microglia to acquire phenotypic and functional properties of mature DCs under similar inducing conditions. Treated adult and fetal microglia became CD14^low and acquired limited expression of CD209 (DC-SIGN); they remained CD1a^– and CD83^–, and decreased MHCII expression, suggesting that they had not achieved a complete DC phenotype. The monocyte-derived DCs efficiently promoted CD4 T cell proliferation in an allogeneic MLR, whereas differentiated adult microglia had a decreased ability to stimulate CD4 T cell proliferation compared with their untreated counterparts. Differentiated fetal microglia did support CD4 T cell proliferation, whereas untreated cells could not. Fetal and adult microglia produced significant amounts of IL-10 following differentiation but no detectable IL-12 p70, in contrast to differentiated monocytes that produced IL-12 p70. Our data indicate that neither adult nor fetal microglia acquired the full characteristic phenotype of mature stimulatory DCs when treated with DC-inducing cytokines in vitro. Moreover, such treatment, especially of adult microglia, induces functional responses that could promote an antiinflammatory environment in the CNS.

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 Research financial support was received from the Multiple Sclerosis Society of Canada, the Canadian Institute for Health Research to J.P.A. C.L. is recipient of a Neuroinflammation Training Award. J.D. is supported by a Research Scholar award from the Fonds de la Recherche en Santé du Québec. N.A. is supported by a Senior Research Fellowship from the Canadian Institute for Health Research. A.B.O. is recipient of the Donald Paty Career Scientist Award of the Multiple Sclerosis Society of Canada.

² Address correspondence and reprint requests to Dr. Jack P. Antel, Neuroimmunology Unit, Montreal Neurological Institute, 3801 University, Room 111, Montréal, Québec H3A 2B4, Canada. E-mail address: jack.antel{at}mcgill.ca

³ Abbreviations used in this paper: MS, multiple sclerosis; EAE, experimental autoimmune encephalomyelitis; DC, dendritic cell; MFI, mean fluorescence intensity.