期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 290, 期 27, 页码 16797-16811出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M115.661272
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资金
- Institut National du Cancer Grant INCa-DHOS
- Ligue Nationale Contre le Cancer (Comite du Val de Marne)
- Association Nationale Recherche-Technologie
- Association pour la Recherche Contre le Cancer
- Grants-in-Aid for Scientific Research [25460592] Funding Source: KAKEN
Galectin-9 (gal-9) is a multifunctional beta-galactoside-binding lectin, frequently released in the extracellular medium, where it acts as a pleiotropic immune modulator. Despite its overall immunosuppressive effects, a recent study has reported bimodal action of gal-9 on human resting blood T cells with apoptosis occurring in the majority of them, followed by a wave of activation and expansion of Th1 cells in the surviving population. Our knowledge of the signaling events triggered by exogenous gal-9 in T cells remains limited. One of these events is cytosolic calcium (Ca2+) release reported in some murine and human T cells. The aim of this study was to investigate the contribution of Ca2+ mobilization to apoptotic and nonapoptotic effects of exogenous gal-9 in human T cells. We found that the T cell receptor (TCR)-CD3 complex and the Lck kinase were required for Ca2+ mobilization but not for apoptosis induction in Jurkat cells. These data were confirmed in human CD4(+) T cells from peripheral blood as follows: a specific Lck chemical inhibitor abrogated Ca2+ mobilization but not apoptosis induction. Moreover, Lck activity was also required for the production of Th1-type cytokines, i.e. interleukin-2 and interferon-gamma, which resulted from gal-9 stimulation in peripheral CD4(+) T cells. These findings indicate that gal-9 acts on T cells by two distinct pathways as follows: one mimicking antigen-specific activation of the TCR with a mandatory contribution of proximal elements of the TCR complex, especially Lck, and another resulting in apoptosis that is independent of this complex.
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