Effect of IVIg on human dendritic cell-mediated antigen uptake and presentation: Role of lipid accumulation Shivashankar Othy a, b , Patrick Bruneval f, g , Selma Topçu a, b , Isabelle Dugail a, c, e , Francisco Delers a, d, e , Sebastien Lacroix-Desmazes a, b, e, h , Jagadeesh Bayry a, b, e, h, * , Srini V. Kaveri a, b, e, h, * a Institut National de la Sante et de la Recherche Medicale, Unité 872, 15 rue de l’Ecole de Médicine, Paris-75006, France b Equipe 16-Immunopathology & therapeutic immunointervention, Centre de Recherche des Cordeliers, Université Pierre et Marie Curie e Paris 6, UMR S 872, Paris-75006, France c Equipe 8-Pathologies nutritionnelles et métaboliques, obésité et diabète, Centre de Recherche des Cordeliers, Université Pierre et Marie Curie e Paris 6, UMR S 872, Paris-75006, France d Equipe 4-Différenciation intestinale et métabolisme lipidique, Centre de Recherche des Cordeliers, Université Pierre et Marie Curie e Paris 6, UMR S 872, Paris-75006, France e Université Paris Descartes, UMR S 872, Paris, France f Institut National de la Sante et de la Recherche Medicale Unité 970, Paris, France g Paris-Centre de Recherche Cardiovasculaire, Paris, France h International Associated Laboratory IMPACT (Institut National de la Santé et de la Recherche Médicale, France e Indian Council of Medical Research, India), National Institute of Immunohaematology, Mumbai, India article info Article history: Received 16 May 2012 Accepted 20 May 2012 Keywords: Autoimmunity Dendritic cells Antigen presentation Intravenous immunoglobulin Lipids abstract Intravenous immunoglobulin (IVIg) is a therapeutic preparation consisting of pools of normal, poly- specific IgG antibodies obtained from plasma of several thousand healthy individuals. In addition to its use in primary and secondary immune deficiency, IVIg is increasingly used in the therapy of a large number of autoimmune conditions. Despite its successful use in immunopathologies for over two decades, the precise mechanisms underlying the therapeutic benefit have not been fully elucidated. We and others have demonstrated that IVIg inhibits the antigen uptake and presentation by dendritic cells (DC). Here we report that IVIg-mediated inhibition of uptake and processing of antigens is associated with an increased accumulation of lipid as analyzed by flow cytometry and electron microscopy. As accumulation of lipids in DC is known to impart tolerogenic properties, these findings unravel novel link between antibodies and intracellular physiology of innate cells and may further uncover novel immu- noregulatory mechanisms of IVIg in auto-inflammatory diseases. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction Dendritic cells (DC) are the professional antigen presenting cells (APC) that are specialized in antigen uptake, processing and presentation [1]. Antigen-primed DC enter a developmentally programmed process of “maturation” which is characterized by up- regulation of various co-stimulatory molecules and secretion of cytokines [1]. DC capture antigen in the periphery and migrate to secondary lymphoid organs where they prime naive T cells [2]. Naïve CD4 Tcells are polarized into various subsets (Th1, Th2, Th17 and iTregs) with a combinatorial code of co-stimulatory molecules and cytokines. Thus, DC direct the events that follow the fate of immune response and dysregulated DC functions are associated with breaking of tolerance to the self and leading to immune disorders. Auto-inflammatory diseases affect about 3% of the world pop- ulation and are caused by various reasons such as genetic, epige- netic and environmental factors [3e17] Because of these causative factors the functions of immune cells are dysregulated. Several immunotherapeutics have been developed to treat these autoim- mune diseases [18,19]. IVIg is a therapeutic preparation of normal human polyclonal IgG obtained from the pools of plasma from a large number of healthy blood donors [20,21]. Initially used as replacement therapy for patients with immune deficiencies, IVIg is now widely used for the treatment of a large number of autoim- mune and systemic inflammatory diseases [15,22e26]. IVIg exerts its beneficial effects by several mutually non-exclusive mechanisms * Corresponding authors. Inserm U 872, Centre de Recherche des Cordeliers, Equipe 16 Immunopathology and therapeutic immunointervention, 15, Rue de l’Ecole de Medecine, Paris-75006, France. Tel.: þ33 1 44 27 82 01/03; fax: þ33 1 44 27 81 94. E-mail addresses: jagadeesh.bayry@crc.jussieu.fr (J. Bayry), srini.kaveri@ crc.jussieu.fr (S.V. Kaveri). Contents lists available at SciVerse ScienceDirect Journal of Autoimmunity journal homepage: www.elsevier.com/locate/jautimm 0896-8411/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.jaut.2012.05.013 Journal of Autoimmunity xxx (2012) 1e5 Please cite this article in press as: Othy S, et al., Effect of IVIg on human dendritic cell-mediated antigen uptake and presentation: Role of lipid accumulation, Journal of Autoimmunity (2012), doi:10.1016/j.jaut.2012.05.013