Fermino, M.L.; Dylon, L.S.D.; Cecílio, N.T.; Santos, S.N.; Toscano, M.A.; Dias-Baruffi, M.; Roque-Barreira, M.C.; Rabinovich, G.A.; Bernardes, E.S. "Lack of galectin-3 increases Jagged1/Notch activation in bone marrow-derived dendritic cells and promotes dysregulation of T helper cell polarization" (2016) Molecular Immunology. 76:22-34
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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. © 2016 Elsevier Ltd.


Documento: Artículo
Título:Lack of galectin-3 increases Jagged1/Notch activation in bone marrow-derived dendritic cells and promotes dysregulation of T helper cell polarization
Autor:Fermino, M.L.; Dylon, L.S.D.; Cecílio, N.T.; Santos, S.N.; Toscano, M.A.; Dias-Baruffi, M.; Roque-Barreira, M.C.; Rabinovich, G.A.; Bernardes, E.S.
Filiación:Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Universidade de São Paulo, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Ribeirão Preto, Brazil
Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Cientificas y Técnicas, Buenos Aires, C1428, Argentina
Departamento de Biologia Celular e Molecular, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil
Nuclear Energy Research Institute, Radiopharmacy Center, São Paulo, Brazil
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, C1428, Argentina
Palabras clave:Galectin-3; Leishmania major; Notch signaling; T helper response; beta actin; delta like 4 protein; galectin 3; gamma interferon; glycoprotein p 15095; interleukin 10; interleukin 12p40; interleukin 1beta; interleukin 4; interleukin 6; Jagged1; Jagged2 protein; messenger RNA; Notch1 receptor; transcription factor GATA 3; transcription factor HES 1; transcription factor T bet; unclassified drug; galectin 3; Jag1 protein, mouse; Notch receptor; protein Jagged 1; animal cell; animal experiment; animal model; animal tissue; Article; bone marrow derived dendritic cell; controlled study; cytokine production; cytokine release; down regulation; foot pad; infection sensitivity; leishmaniasis; lymph node; mouse; nonhuman; polarization; priority journal; signal transduction; T lymphocyte activation; Th1 cell; Th1 Th2 balance; Th2 cell; upregulation; animal; Bagg albino mouse; bone marrow cell; cell differentiation; dendritic cell; disease model; flow cytometry; helper cell; immunology; knockout mouse; Leishmania major; metabolism; real time polymerase chain reaction; skin leishmaniasis; Western blotting; Animals; Blotting, Western; Bone Marrow Cells; Cell Differentiation; Dendritic Cells; Disease Models, Animal; Flow Cytometry; Galectin 3; Jagged-1 Protein; Leishmania major; Leishmaniasis, Cutaneous; Mice; Mice, Inbred BALB C; Mice, Knockout; Real-Time Polymerase Chain Reaction; Receptors, Notch; T-Lymphocytes, Helper-Inducer
Página de inicio:22
Página de fin:34
Título revista:Molecular Immunology
Título revista abreviado:Mol. Immunol.
CAS:galectin 3, 208128-56-7; gamma interferon, 82115-62-6; transcription factor GATA 3, 137878-55-8; Galectin 3; Jag1 protein, mouse; Jagged-1 Protein; Receptors, Notch


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---------- APA ----------
Fermino, M.L., Dylon, L.S.D., Cecílio, N.T., Santos, S.N., Toscano, M.A., Dias-Baruffi, M., Roque-Barreira, M.C.,..., Bernardes, E.S. (2016) . Lack of galectin-3 increases Jagged1/Notch activation in bone marrow-derived dendritic cells and promotes dysregulation of T helper cell polarization. Molecular Immunology, 76, 22-34.
---------- CHICAGO ----------
Fermino, M.L., Dylon, L.S.D., Cecílio, N.T., Santos, S.N., Toscano, M.A., Dias-Baruffi, M., et al. "Lack of galectin-3 increases Jagged1/Notch activation in bone marrow-derived dendritic cells and promotes dysregulation of T helper cell polarization" . Molecular Immunology 76 (2016) : 22-34.
---------- MLA ----------
Fermino, M.L., Dylon, L.S.D., Cecílio, N.T., Santos, S.N., Toscano, M.A., Dias-Baruffi, M., et al. "Lack of galectin-3 increases Jagged1/Notch activation in bone marrow-derived dendritic cells and promotes dysregulation of T helper cell polarization" . Molecular Immunology, vol. 76, 2016, pp. 22-34.
---------- VANCOUVER ----------
Fermino, M.L., Dylon, L.S.D., Cecílio, N.T., Santos, S.N., Toscano, M.A., Dias-Baruffi, M., et al. Lack of galectin-3 increases Jagged1/Notch activation in bone marrow-derived dendritic cells and promotes dysregulation of T helper cell polarization. Mol. Immunol. 2016;76:22-34.