Differential sialylation dictates the fate of regulatory T cells

Event Abstract Back to Event Differential sialylation dictates the fate of regulatory T cells Santiago P. Mendez Huergo1*, Tomas D´Alotto Moreno1, Marta A. Toscano1, Juan P. Cerliani1, Diego O. Croci Russo1, Karina V. Mariño1 and Gabriel A. Rabinovich1 1 Instituto de biologia y medicina experimental, Argentina Galectin-1 (Gal-1), an endogenous lectin found at sites of inflammation and tumor growth, plays key roles in immune tolerance and homeostasis. This lectin specifically interacts with lactosamine-enriched N-glycans and core-2-O-glycans on cell surface glycoproteins. Here we investigated the impact of Gal1-glycan interactions in the physiology of regulatory T (Treg) cells. Using a panel of plant lectins, we analyzed the glycosylation profile of naturally-occurring Treg cells (nTregs) isolated from the spleen of C57BL/6 mice. Glycophenotypic analysis revealed higher frequency of asialo-core-1-O-glycans and complex N-glycans with terminal a2-3-linked sialic acid (SA) on LacNAc residues on nTregs. This effect was accompanied by the presence of large amounts of a2-6-linked sialic acid (SAa2-6), a glyco-epitope that is restrictive for Gal1 binding in both nTregs and inducible Tregs (iTregs), versus to Tact cells. Similar results were obtained using lectin binding assays and mass spectrometric analysis. Notably, iTregs exhibited lower capacity to bind Gal1 compared to Tact cells (p<0,01), and increased expression of the a-2,6-sialyltransferase 1 (ST6Gal1), an enzyme responsible of incorporating SAa2-6 residues. When naive CD4+T cells were differentiated into iTregs, binding of Gal1 decreased and SAα-2,6 increased in a time-dependent manner. In an in vivo model, effector T cells from mice immunized with ovalbumin (OVA) exhibited a higher capacity to bind Gal1 as compared to iTregs (p<0,01). Moreover, iTregs were considerably more resistant to Gal1-induced cell death than Th17 and Tact cells. Our results uncover a glycosylation-dependent mechanism which selectively dictates the fate of Treg cells. References Vignali, D. A., L. W. Collison, et al. 2008. How regulatory T cells work. Nat Rev Immunol 8(7): 523-32. Valencia, X. and P. Lipsky 2007. CD4+CD25+FoxP3+ regulatory T cells in autoimmune diseases. Nat Clin Pract Rheumatol 3: 619-26. Garin, M.I., et al. 2007. Galectin-1: a key effector of regulation mediated by CD4+CD25+ T cells. Blood 109:2058-2065. Toscano, M. A., et al. 2007. Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death. Nat Immunol 8:825-834 Rabinovich G and Toscano M (2009). Turning 'sweet' on immunity: galectin-glycan interactions in immune tolerance and inflammation. Nat Rev Immunol. 2009 9:338-52. Keywords: Regultaory T cells, Galectin 1, Glycosilation, sialylation, Apoptosis Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Adaptive Immunity Citation: Mendez Huergo SP, D´Alotto Moreno T, Toscano MA, Cerliani JP, Croci Russo DO, Mariño KV and Rabinovich GA (2013). Differential sialylation dictates the fate of regulatory T cells. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00454 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: 17 Apr 2013; Published Online: 22 Aug 2013. * Correspondence: Mr. Santiago P Mendez Huergo, Instituto de biologia y medicina experimental, Buenos Aires, Argentina, santiago.mendezhuergo@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 Santiago P Mendez Huergo Tomas D´Alotto Moreno Marta A Toscano Juan P Cerliani Diego O Croci Russo Karina V Mariño Gabriel A Rabinovich Google Santiago P Mendez Huergo Tomas D´Alotto Moreno Marta A Toscano Juan P Cerliani Diego O Croci Russo Karina V Mariño Gabriel A Rabinovich Google Scholar Santiago P Mendez Huergo Tomas D´Alotto Moreno Marta A Toscano Juan P Cerliani Diego O Croci Russo Karina V Mariño Gabriel A Rabinovich PubMed Santiago P Mendez Huergo Tomas D´Alotto Moreno Marta A Toscano Juan P Cerliani Diego O Croci Russo Karina V Mariño Gabriel A Rabinovich 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.