CONICET | Buscador de Institutos y Recursos Humanos

Galectin-1 (Gal1), a glycan-binding protein that recognizes N-acetyllactosamine residues in membrane glycoproteins and the extracellular matrix, is a key regulator of immune cell homeostasis. It has been demonstrated that different effector profiles of helper T cells, exhibit a specific glycosylation profile and a differential susceptibility to Gal-1 binding; being those of pro-inflammatory nature (Th1 and Th17) preferential targets of this lectin and those of a Th2 or Treg nature, resistant to this endogenous lectin. However, it is still unknown how this lectin affects the fate and function of follicular helper T cells (Thf), key cells in the development of the humoral responses. These cells are essential for germinal center formation, production of high affinity antibodies and differentiation of long-lived plasma cells and memory B cells. Here we aimed to study the role of Gal-1-glycan interactions in the biology of Thf. An In vitro differentiation protocol was set up by stimulating splenic naïve CD4+ T cells from WT and Gal1-deficient (Lgals1 -/-) mice, with recombinant IL-6 and IL-21 and neutralizing antibodies against IL-4, IL-12, IFN-γ, and TGF-β. To study Thf cells in vivo, we immunized mice with BSA-TNP subcutaneously and, after 7 days, analyzed the Thf cell population as CD4+ CXCR5+ PD1+ cells in draining lymph nodes. We found that after immunization, Lgals1-/- mice displayed higher percentageof Thf cells than WT mice. In addition, Thf cells showed a particular glycosylation profile characterized by increased poly-lactosamine residues and beta-1,6-branched complex N-glycans, consistent with a glycophenotype permissive for Gal1 binding. These results suggest that Gal1 may control the fate and function of Thf cells during the development of antibody-mediated responses.