Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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

Proceedings of the National Academy of Sciences of the United States of America

Publication Date

12/08/2009

Volume

106

Pages

14496 - 14501

Addresses

Department of Dermatology, School of Medicine, University of California at Davis, Sacramento, CA 95817, USA.

Keywords

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