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Regulated expression of galectin-1 during T-cell activation involves Lck and Fyn kinases and signaling through MEK1/ERK, p38 MAP kinase and p70S6 kinase

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Abstract

Recent evidence has implicated galectins and their carbohydrate ligands as novel regulators of T-cell homeostasis. Galectin-1 (Gal-1), a member of this family, inhibits clonal expansion, induces apoptosis of antigen-primed T lymphocytes and suppresses the development of T-cell-mediated autoimmune diseases in vivo. Because the β-galactoside-binding protein is expressed in activated but not resting T cells, it has been hypothesized that Gal-1-induced apoptosis may constitute an autocrine suicide mechanism to eliminate activated T cells contributing to the termination of an effector immune response. We undertook this study to investigate the signals and intracellular pathways leading to Gal-1 expression during T-cell activation. When T cells were stimulated either with anti-CD3 or anti-CD28 monoclonal antibody plus PMA in the presence of accessory cells, a sustained up-regulation of Gal-1 was observed, reaching a plateau between days 3 and 5 following CD3 engagement or costimulation through CD28. Investigation of the signal transduction events involved in this process revealed a role for Lck and Fyn kinases, since the Src kinase inhibitor PP1 inhibited the up-regulated expression of Gal-1 following T-cell activation. Downstream signaling routes involve mitogen-activated protein kinase (MAPK) kinase (MEK)1/extracellular signal-regulated kinase (ERK) and p38 MAPK, as Gal-1 expression was prevented by U0126 and SB202190. In addition, expression of Gal-1 involves interleukin (IL)-2-dependent signaling routes triggered by p70S6 kinase, as it could be inhibited by rapamycin. This is the first demonstration of the intracellular pathways that control activation-induced expression of Gal-1, which may reveal potential targets for immune intervention to modulate expression of this β-galactoside-binding protein in pathological disorders. (Mol Cell Biochem 267: 177–185, 2004)

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Authors and Affiliations

  1. Division of Immunogenetics, Hospital de Clínicas “José de San Martín”, Department of Microbiology, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina

    Mercedes B. Fuertes, Luciana L. Molinero, Marta A. Toscano, Juan M. Ilarregui, Natalia Rubinstein, Leonardo Fainboim, Norberto W. Zwirner & Gabriel A. Rabinovich

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  1. Mercedes B. Fuertes
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  2. Luciana L. Molinero
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  3. Marta A. Toscano
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  4. Juan M. Ilarregui
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  8. Gabriel A. Rabinovich
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Fuertes, M.B., Molinero, L.L., Toscano, M.A. et al. Regulated expression of galectin-1 during T-cell activation involves Lck and Fyn kinases and signaling through MEK1/ERK, p38 MAP kinase and p70S6 kinase. Mol Cell Biochem 267, 177–185 (2004). https://doi.org/10.1023/B:MCBI.0000049376.50242.7f

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