Galectin immunomodulation: Control of T cell viability and dendritic cell maturation.

摘要

Galectins are a family of carbohydrate binding proteins with profound immunomodulatory activity. Galectin-1 and -3 both regulate viability of T cells and cancer cells. Extracellular galectin-1 directly induces apoptosis of T cells, thymocytes, and some tumor cells. In contrast, intracellular expression of galectin-3 prevents apoptosis of T cells and tumor cells. We demonstrate that extracellular galectin-3 directly induces apoptosis of T cells and thymocytes through binding to cell surface glycoprotein receptors. To begin to elucidate the galectin-3 death pathway, we identify galectin-3 counter-receptors from T cells and examine the cell surface events subsequent to galectin-3 binding.; In addition to direct effects of galectins on many cell types, galectin family members influence the overall nature of the immune response. Galectin-1 typically shifts the balance towards a Th2 response, while galectin-3 shifts the balance towards a Th1 response. However, little is known about the cell types mediating these effects and the direct effects of galectin binding to these cells. Dendritic cells function at the interface between the innate and adaptive immune responses. Dendritic cells recognize pathogens, internalize antigen, and display the antigen to naive T cells. During this process, dendritic cells mature, secreting cytokines and expressing cell surface molecules involved in the differentiation of naive T cells into distinct effector subsets, ultimately determining the nature of the immune response. We identify galectin-1 as a novel inducer of dendritic cell maturation, initiating changes in expression of dendritic cell surface molecules and secreted cytokines involved in the activation and differentiation of naive T cells.; Through our studies of galectin-1 and -3 we have identified two distinct mechanisms of galectin immunomodulation, galectin-1 and -3 induction of T cell death and galectin-1 maturation of dendritic cells. As galectins induce many immunomodulatory effects in diverse immune cell types, it appears that galectins function as master regulators of the immune response. As already demonstrated in several animal models of disease, a greater understanding of the effects and mechanisms of galectin family members on specific immune cell types and the overall immune response has the potential for development of galectin based therapy for treatment of immune mediated disease.