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Lack of galectin-3 increases Jagged1/Notch activation in bone marrow-derived dendritic cells and promotes dysregulation of T helper cell polarization.
Fermino, Marise L; Dylon, L Sebastian D; Cecílio, Nerry T; Santos, Sofia N; Toscano, Marta A; Dias-Baruffi, Marcelo; Roque-Barreira, Maria C; Rabinovich, Gabriel A; Bernardes, Emerson S.
Afiliação
  • Fermino ML; Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
  • Dylon LS; Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Cientificas y Técnicas, C1428 Buenos Aires, Argentina.
  • Cecílio NT; Departamento de Biologia Celular e Molecular, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
  • Santos SN; Nuclear Energy Research Institute, Radiopharmacy Center, São Paulo, Brazil.
  • Toscano MA; Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Cientificas y Técnicas, C1428 Buenos Aires, Argentina.
  • Dias-Baruffi M; Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
  • Roque-Barreira MC; Departamento de Biologia Celular e Molecular, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
  • Rabinovich GA; Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Cientificas y Técnicas, C1428 Buenos Aires, Argentina; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428 Buenos Air
  • Bernardes ES; Nuclear Energy Research Institute, Radiopharmacy Center, São Paulo, Brazil. Electronic address: ebernardes@ipen.br.
Mol Immunol ; 76: 22-34, 2016 08.
Article em En | MEDLINE | ID: mdl-27344022
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Dendríticas / Linfócitos T Auxiliares-Indutores / Galectina 3 / Receptores Notch / Proteína Jagged-1 Limite: Animals Idioma: En Revista: Mol Immunol Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Dendríticas / Linfócitos T Auxiliares-Indutores / Galectina 3 / Receptores Notch / Proteína Jagged-1 Limite: Animals Idioma: En Revista: Mol Immunol Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido