Lack of galectin-3 increases Jagged1/Notch activation in bone marrow-derived dendritic cells and promotes dysregulation of T helper cell polarization

Author(s)

Fermin, Marise L. ; Dylon, L. Sebastian D. ; Cecilio, Nerry T. ; Santos, Sofia N. ; Toscano, Marta A. ; Dias-Baruffi, Marcelo ; Roque-Barreira, Maria C. ; Rabinovich, Gabriel A. ; Bernardes, Emerson S.

• Document type: Journal article
• Source: Molecular Immunology; v. 76, p. 22-34, AUG 2016.
• Web of Science Citations: 8

Abstract

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, Jaggedl, Jaggedl 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 Jaggedl and pro-inflammatory cytokines. In addition, activation of Notch signaling in BMDCs upon stimulation with Jaggedl 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 Lgals3-1- BMDCs partially reverted the increased sensitivity to Jaggedl 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. (C) 2016 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 12/06875-6 - Development and production of positron emission tomography radiopharmaceuticals for diagnostic purposes in oncology
• Grantee: Emerson Soares Bernardes
• Support Opportunities: Research Grants - Young Investigators Grants