INVESTIGADORES
FAINBOIM Leonardo
artículos
Título:
Regulated expression of galectin-1 during T cell activation involves Lck and Fyn kinases and signaling through MEK1/ERK, p38 MAP kinase and p7056 kinase
Autor/es:
M. FUERTES ; L. MOLINERO ; M. A. TOSCANO ; J. M. ILARREGUI ; N. RUBINSTEIN ; L. FAINBOIM ; N. W. ZWIRNER ; G. A. RABINOVICH
Revista:
MOLECULAR AND CELLULAR BIOCHEMISTRY
Editorial:
SPRINGER
Referencias:
Lugar: Berlin; Año: 2004 vol. 30 p. 1 - 9
ISSN:
0300-8177
Resumen:
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 upregulation 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 expressionwas 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.