Differential sialylation dictates the fate of regulatory T cells
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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
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Valencia, X. and P. Lipsky 2007. CD4+CD25+FoxP3+ regulatory T cells in autoimmune diseases. Nat Clin Pract Rheumatol 3: 619-26.
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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
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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
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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