Dimeric galectin‐1 induces IL‐10 production in T‐lymphocytes: an important tool in the regulation of the immune response

Abstract

Galectin-1, a beta-galactoside binding protein that can occur as both a monomer and a homodimer, binds to leucocyte membrane antigens such as CD7, CD43, and CD45, and has immune-regulatory functions in several animal models of autoimmune disease. However, its mechanism of action is only partially understood. In this study, a marked increase in IL-10 mRNA and protein levels was demonstrated in non-activated and activated CD4(+) and CD8(+) T-cells, following treatment with a high concentration (dimeric form), but not a low concentration (monomeric form), of recombinant galectin-1 protein. IL-10 is known to suppress TH1 type immune responses and upregulation of IL-10 may thus contribute to the immune-regulatory function of galectin-1. Galectin-1 was strongly expressed on the endothelial cells of human kidney allografts, suggesting a role in the regulation of immune responses in transplantation. Administration of high concentrations of galectin-1 may be a useful tool in the treatment of T-cell-mediated diseases.

Differential Roles of Galectin-1 and Galectin-3 in Regulating Leukocyte Viability and Cytokine Secretion

“…Subsequent studies suggested that Gal-1 may modulate the immune system by inducing cell death in activated T cells (23). The results of the present study suggest that the in vivo effects of Gal-1 may result from altered expression of IL-10 and IFN-␥ in T cells as opposed to directly altering T cell viability, consistent with previous results (48). IL-10 exhibits potent immunosuppressive activity, inhibiting T cell activation and Th1 cytokine secretion and decreasing costimulatory receptors on APCs (67,68).…”

“…Furthermore, iGal-1 retained the carbohydratebinding specificity of Gal-1. More importantly, iGal-1 retained previously documented biological endpoints of Gal-1 activity on leukocytes, including the induction of PS exposure in activated neutrophils, MOLT-4 cells and CEM cells in the absence of cell death (26,29,30), the induction of Ca 2ϩ flux in activated neutrophils (30), the induction of apoptosis in T cells, CEM cells and MOLT-4 cells in the presence of DTT (23,24,26,46,79) and the ability to alter T cell cytokine production (48). Taken together, these results demonstrate that iGal-1 retains the biological activities of the Gal-1.…”

“…To eliminate artificial effects introduced by DTT inclusion (23,26,(35)(36)(37)(38), while controlling for potential loss of Gal-1 activity, we stabilized Gal-1 with iodoacetamide which was previously shown to protect Gal-1 from oxidative inactivation (39 -44). In this study, iodoacetamidetreated Gal-1 (iGal-1) retained key biological activities previously documented for the unmodified protein (23,26,29,(45)(46)(47)(48), demonstrating that iGal-1 retains function while resisting oxidative inactivation. Furthermore, these results demonstrate that the failure of unmodified Gal-1 to induce apoptotic death in previous studies (26,29,30) was not a reflection of activity loss.…”

“…Few studies have examined the effects of Gal-1 in the absence of DTT. However, Gal-1 has been shown to increase IL-10 production and attenuate IFN-␥ production in the absence of DTT (48). We next sought to determine whether iGal-1 induced the same effects.…”

Psoriasis in humans is associated with down‐regulation of galectins in dendritic cells

“…In vitro studies revealed that gal-1 limits the immune response, for example promoting apoptosis of Th-1 cells, inducing IL-10, or down-regulating pro-inflammatory cytokines [3,4].…”