Estrogen receptor signaling and X-chromosome complement both independently contribute to the enhanced TLR-7-mediated responses of woman plasmacytoid dendritic cells

Abstract

Event Abstract Back to Event Estrogen receptor signaling and X-chromosome complement both independently contribute to the enhanced TLR-7-mediated responses of woman plasmacytoid dendritic cells Sophie LAFFONT1*, Nelly Rouquié1, Cyril Seillet1, Joel Plumas2, Caroline Aspord2 and Jean-Charles Guéry1 1 Centre de Physiopathologie de Toulouse Purpan - Inserm U1043, CHU Purpan, France 2 Institut ALbert Bonniot - Inserm U823, France Human plasmacytoid dendritic cells (pDCs) play a major role in innate immunity through the production of type I IFNs after Toll-like receptor (TLR) engagement by pathogens. Woman pDCs exhibit enhanced TLR-7-mediated responses as compared to man pDCs, which may account for sex-based differences in autoimmune and infectious diseases. To further characterize the mechanisms underlying this sex-based difference in pDC innate functions, we investigated the respective contribution of X chromosome dosage versus sex hormones using a humanized mouse model in which male or female NOD-SCID-ß2m-/- mice were transplanted with human progenitor cells (HPCs) purified from either male or female donors. We showed that the frequency of IFN-α- and TNF-α-producing pDCs in response to TLR-7 ligands was enhanced in female mice as compared to male, suggesting that endogenous estrogens positively regulated TLR responses in pDCs in agreement with our recently published work (Seillet et al., Blood 2012 119:454). Indeed, using an in vitro model of Flt3L/IL-7-driven human pDC differentiation from HPCs, we demonstrated that blockade of ER-signaling during pDC development inhibited TLR-7 and TLR-9-mediated IFN-a production by human pDCs from either sex. Lastly, by comparing the innate functions of female or male human pDCs that develop in HIS mice, we observed that female pDCs have an enhanced TLR-7-mediated IFN-α response as compared to male ones, irrespective of the sex of the recipient mice in which they developed. Taken together, these results indicate that cell-intrinsic ER-signaling and X chromosome complement both independently contribute to the enhanced TLR-mediated responses of woman pDCs. Keywords: Estr, estrogen receptor, pDCs, sex differences, TLRs (Toll-like receptors) Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Innate immunity Citation: LAFFONT S, Rouquié N, Seillet C, Plumas J, Aspord C and Guéry J (2013). Estrogen receptor signaling and X-chromosome complement both independently contribute to the enhanced TLR-7-mediated responses of woman plasmacytoid dendritic cells. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00954 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Sophie LAFFONT, Centre de Physiopathologie de Toulouse Purpan - Inserm U1043, CHU Purpan, Toulouse, 31024 Toulouse Cedex 03, France, sophie.laffont-pradines@inserm.fr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Sophie LAFFONT Nelly Rouquié Cyril Seillet Joel Plumas Caroline Aspord Jean-Charles Guéry Google Sophie LAFFONT Nelly Rouquié Cyril Seillet Joel Plumas Caroline Aspord Jean-Charles Guéry Google Scholar Sophie LAFFONT Nelly Rouquié Cyril Seillet Joel Plumas Caroline Aspord Jean-Charles Guéry PubMed Sophie LAFFONT Nelly Rouquié Cyril Seillet Joel Plumas Caroline Aspord Jean-Charles Guéry Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.