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We have investigated the function of endogenous galectin-3 in T cells. Galectin-3-deficient (gal3(-/-)) CD4(+) T cells secreted more IFN-gamma 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 publication

DOI

10.1073/pnas.0903497106

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

25/08/2009

Volume

106

Pages

14496 - 14501

Keywords

Animals, CD4-Positive T-Lymphocytes, Calcium-Binding Proteins, Cell Cycle Proteins, Cell Line, Endosomal Sorting Complexes Required for Transport, Galectin 3, Humans, Immunoblotting, Immunological Synapses, Immunoprecipitation, Interferon-gamma, Interleukin-4, Jurkat Cells, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Protein Binding, Receptors, Antigen, T-Cell, Signal Transduction, Transfection, Two-Hybrid System Techniques