Inhibins regulate peripheral Treg induction through modulation of dendritic cell function.

Abstract

Event Abstract Back to Event Inhibins regulate peripheral Treg induction through modulation of dendritic cell function. SANDRA ORTEGA1*, Marisol De La Fuente Granada1, Roxana Olguín Alor1, Jesús Ramsés Chávez-Ríos1, Laura Bonifaz Alfonso2, Eduardo A. García-Zepeda1 and Gloria Soldevila Melgarejo1 1 UNAM, Depto de Inmunología, Instituto de Investigaciones Biomédicas, Mexico 2 Centro Médico Nacional Siglo XXI, IMSS, Mexico Inhibins and Activins, members of the Transforming Growth Factorb superfamily, participate in the immune system as key regulators of several cellular functions. Despite some reports indicate that Activins may regulate DC maturation and function, the role of Inhibins in these processes remains elusive. Here, we investigated the role of Inhibins in DC maturation and function and its impact in Treg induction and Th effector differentiation. Analysis of mature Inhα-/- BMDCs obtained after lipopolysaccharide (LPS) stimulation (mBMDC) showed a significant reduction in the surface expression of MHC II and CD86 (a semi-mature phenotype), and a concomitant increase in PD-L1, compared to WT mBMDC. In addition, the Inhα-/- mBMDC showed reduced migration towards CCL19 and CCL21 both in vitro chemotaxis assays as well as and in vivo, in in vivo adoptive competitive transfer assays, in comparison to WT. To evaluate if these findings correlated with a “tolerogenic” phenotype, functional responses were assayed showing that mBMDC from Inhα-/- displayed reduced capacity to induce proliferation of allogeneic CD4+ naïve T cells. This correlated with an increased induction of iTregs (CD25+Foxp3+) from CD4+ naïve T cells in the presence of low concentrations of anti-CD3 and TGFb as well as with increased absolute numbers of iTregs and nTreg (CD4+CD25+Foxp3+Helios- and Helios+, respectively) in peripheral lymph nodes of 4 week-old Inhα-/- mice compared to WT. Interestingly, Inhα-/- T cells showed a reduced induction of Tregs in the absence of APCs, suggesting an intrinsic role of Inhibins in the differentiation of T cells. Analysis of Th effector differentiation is currently being performed using an OVA-specific transgenic mouse model. Our data demonstrate for the first time a direct role of Inhibins in the regulation of DC mediated functions and point out the importance of Inhibin signaling to maintain the balance between inflammation and tolerance. Acknowledgements Work supported by PAPIIT, DGAPA, UNAM (Grant IN209615). Keywords: Inhibins, T cells diferentiation, Dendritic cells function, T regs induction, Dendritic cells maturation Conference: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015. Presentation Type: Poster Presentation Topic: Adaptive Immunity Citation: ORTEGA S, De La Fuente Granada M, Olguín Alor R, Chávez-Ríos J, Bonifaz Alfonso L, García-Zepeda E and Soldevila Melgarejo G (2015). Inhibins regulate peripheral Treg induction through modulation of dendritic cell function.. Front. Immunol. Conference Abstract: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología. doi: 10.3389/conf.fimmu.2015.05.00374 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: 15 May 2015; Published Online: 16 Sep 2015. * Correspondence: Ms. SANDRA ORTEGA, UNAM, Depto de Inmunología, Instituto de Investigaciones Biomédicas, México, D.F., Mexico, amyrisortega@gmail.com 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 SANDRA ORTEGA Marisol De La Fuente Granada Roxana Olguín Alor Jesús Ramsés Chávez-Ríos Laura Bonifaz Alfonso Eduardo A. García-Zepeda Gloria Soldevila Melgarejo Google SANDRA ORTEGA Marisol De La Fuente Granada Roxana Olguín Alor Jesús Ramsés Chávez-Ríos Laura Bonifaz Alfonso Eduardo A. García-Zepeda Gloria Soldevila Melgarejo Google Scholar SANDRA ORTEGA Marisol De La Fuente Granada Roxana Olguín Alor Jesús Ramsés Chávez-Ríos Laura Bonifaz Alfonso Eduardo A. García-Zepeda Gloria Soldevila Melgarejo PubMed SANDRA ORTEGA Marisol De La Fuente Granada Roxana Olguín Alor Jesús Ramsés Chávez-Ríos Laura Bonifaz Alfonso Eduardo A. García-Zepeda Gloria Soldevila Melgarejo 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.