Lack of galectin-3 increases Jagged1/Notch activation in bone marrow-derived dendritic cells and promotes dysregulation of T helper cell polarization
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Molecular Immunology
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Galectin-3, an endogenous glycan-binding protein, is abundantly expressed at sites of inflammation and immune cell activation. Although this lectin has been implicated in the control of T helper (Th) polarization, the mechanisms underlying this effect are not well understood. Here, we investigated the role of endogenous galectin-3 during the course of experimental Leishmania major infection using galectin-3-deficient (Lgals3−/−) mice in a BALB/c background and the involvement of Notch signaling pathway in this process. Lgals3−/− mice displayed an augmented, although mixed Th1/Th2 responses compared with wild-type (WT) mice. Concomitantly, lymph node and footpad lesion cells from infected Lgals3−/− mice showed enhanced levels of Notch signaling components (Notch-1, Jagged1, Jagged2 and Notch target gene Hes-1). Bone marrow-derived dendritic cells (BMDCs) from uninfected Lgals3−/− mice also displayed increased expression of the Notch ligands Delta-like-4 and Jagged1 and pro-inflammatory cytokines. In addition, activation of Notch signaling in BMDCs upon stimulation with Jagged1 was more pronounced in Lgals3−/− BMDCs compared to WT BMDCs; this condition resulted in increased production of IL-6 by Lgals3−/− BMDCs. Finally, addition of exogenous galectin-3 to Lgals3−/− BMDCs partially reverted the increased sensitivity to Jagged1 stimulation. Our results suggest that endogenous galectin-3 regulates Notch signaling activation in BMDCs and influences polarization of T helper responses, thus increasing susceptibility to L. major infection.
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FERMINO, MARISE L.; DYLON, L.S.D.; CECILIO, NERRY T.; SANTOS, SOFIA N.; TOSCANO, MARTA A.; DIAS-BARUFFI, MARCELO; ROQUE-BARREIRA, MARIA C.; RABINOVICH, GABRIEL A.; BERNARDES, EMERSON S. Lack of galectin-3 increases Jagged1/Notch activation in bone marrow-derived dendritic cells and promotes dysregulation of T helper cell polarization. Molecular Immunology, v. 76, p. 22-34, 2016. DOI: 10.1016/j.molimm.2016.06.005. Disponível em: http://repositorio.ipen.br/handle/123456789/27737. Acesso em: 30 Dec 2025.
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