Lack of galectin-3 increases Jagged1/Notch activation in bone marrow-derived dendritic cells and promotes dysregulation of T helper cell polarization
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 t...
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01615890_v76_n_p22_Fermino http://hdl.handle.net/20.500.12110/paper_01615890_v76_n_p22_Fermino |
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paper:paper_01615890_v76_n_p22_Fermino2023-06-08T15:13:30Z Lack of galectin-3 increases Jagged1/Notch activation in bone marrow-derived dendritic cells and promotes dysregulation of T helper cell polarization Toscano, Marta Alicia 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 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. Fil:Toscano, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01615890_v76_n_p22_Fermino http://hdl.handle.net/20.500.12110/paper_01615890_v76_n_p22_Fermino |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Toscano, Marta Alicia Lack of galectin-3 increases Jagged1/Notch activation in bone marrow-derived dendritic cells and promotes dysregulation of T helper cell polarization |
| topic_facet |
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 |
| description |
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. |
| author |
Toscano, Marta Alicia |
| author_facet |
Toscano, Marta Alicia |
| author_sort |
Toscano, Marta Alicia |
| title |
Lack of galectin-3 increases Jagged1/Notch activation in bone marrow-derived dendritic cells and promotes dysregulation of T helper cell polarization |
| title_short |
Lack of galectin-3 increases Jagged1/Notch activation in bone marrow-derived dendritic cells and promotes dysregulation of T helper cell polarization |
| title_full |
Lack of galectin-3 increases Jagged1/Notch activation in bone marrow-derived dendritic cells and promotes dysregulation of T helper cell polarization |
| title_fullStr |
Lack of galectin-3 increases Jagged1/Notch activation in bone marrow-derived dendritic cells and promotes dysregulation of T helper cell polarization |
| title_full_unstemmed |
Lack of galectin-3 increases Jagged1/Notch activation in bone marrow-derived dendritic cells and promotes dysregulation of T helper cell polarization |
| title_sort |
lack of galectin-3 increases jagged1/notch activation in bone marrow-derived dendritic cells and promotes dysregulation of t helper cell polarization |
| publishDate |
2016 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01615890_v76_n_p22_Fermino http://hdl.handle.net/20.500.12110/paper_01615890_v76_n_p22_Fermino |
| work_keys_str_mv |
AT toscanomartaalicia lackofgalectin3increasesjagged1notchactivationinbonemarrowderiveddendriticcellsandpromotesdysregulationofthelpercellpolarization |
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1768544080383442944 |