Galectin-3 negatively regulates TCR-mediated CD4+ T-cell activation at the immunological synapse

Huan Yuan Chen, Agnes Fermin, Santosh Vardhana, I. Chun Weng, Kin Fong Robin Lo, En Yuh Chang, Emanual Michael Maverakis, Ri Yao Yang, Daniel K. Hsu, Michael L. Dustin, Fu-Tong Liu

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99 Scopus citations

Abstract

We have investigated the function of endogenous galectin-3 in T cells. Galectin-3-deficient (gal3-/-) CD4+ T cells secreted more IFN-γ and IL-4 than gal3+/+CD4+ T cells after T-cell receptor (TCR) engagement. Galectin-3 was recruited to the cytoplasmic side of the immunological synapse (IS) in activated T cells. In T cells stimulated on supported lipid bilayers, galectin-3 was primarily located at the peripheral supramolecular activation cluster (pSMAC). Gal3+/+ T cells formed central SMAC on lipid bilayers less effectively and adhered to antigen-presenting cells less firmly than gal3-/- T cells, suggesting that galectin-3 destabilizes the IS. Galectin-3 expression was associated with lower levels of early signaling events and phosphotyrosine signals at the pSMAC. Additional data suggest that galectin-3 potentiates down-regulation of TCR in T cells. By yeast two-hybrid screening, we identified as a galectin-3-binding partner, Alix, which is known to be involved in protein transport and regulation of cell surface expression of certain receptors. Co-immunoprecipitation confirmed galectin-3-Alix association and immunofluorescence analysis demonstrated the translocation of Alix to the IS in activated T cells. We conclude that galectin-3 is an inhibitory regulator of T-cell activation and functions intracellularly by promoting TCR down-regulation, possibly through modulating Alix's function at the IS.

Original languageEnglish (US)
Pages (from-to)14496-14501
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number34
DOIs
StatePublished - Aug 25 2009

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    Chen, H. Y., Fermin, A., Vardhana, S., Weng, I. C., Lo, K. F. R., Chang, E. Y., Maverakis, E. M., Yang, R. Y., Hsu, D. K., Dustin, M. L., & Liu, F-T. (2009). Galectin-3 negatively regulates TCR-mediated CD4+ T-cell activation at the immunological synapse. Proceedings of the National Academy of Sciences of the United States of America, 106(34), 14496-14501. https://doi.org/10.1073/pnas.0903497106