Galectin-1 Suppresses Autoimmune Retinal Disease by Promoting Concomitant Th2- and T Regulatory-Mediated Anti-Inflammatory Responses

Abstract

Intraocular inflammatory diseases are a common cause of severe visual impairment and blindness. In this study, we investigated the immunoregulatory role of galectin-1 (Gal-1), an endogenous lectin found at sites of T cell activation and immune privilege, in experimental autoimmune uveitis (EAU), a Th1-mediated model of retinal disease. Treatment with rGal-1 either early or late during the course of interphotoreceptor retinoid-binding protein-induced EAU was sufficient to suppress ocular pathology, inhibit leukocyte infiltration, and counteract pathogenic Th1 cells. Administration of rGal-1 at the early or late phases of EAU ameliorated disease by skewing the uveitogenic response toward nonpathogenic Th2 or T regulatory-mediated anti-inflammatory responses. Consistently, adoptive transfer of CD4+ regulatory T cells obtained from rGal-1-treated mice prevented the development of active EAU in syngeneic recipients. In addition, increased levels of apoptosis were detected in lymph nodes from mice treated with rGal-1 during the efferent phase of the disease. Our results underscore the ability of Gal-1 to counteract Th1-mediated responses through different, but potentially overlapping anti-inflammatory mechanisms and suggest a possible therapeutic use of this protein for the treatment of human uveitic diseases of autoimmune etiology.

Functions of cell surface galectin-glycoprotein lattices

“…We found that treatment with recombinant galectin-1 in the efferent phase of autoimmune ocular inflammation results in increased IL-10 and TGF-β production and expansion of regulatory T cells in vivo [43]. Interestingly, recent studies demonstrated that galectin-1 and -10 are overexpressed in regulatory T cells, and are critical for the suppressive activity of these cells [49,50].…”

“…Compelling evidence indicates that galectin-1 treatment suppresses chronic inflammation, modulates T-cell survival and skews the balance towards a Th2 cytokine profile in vitro [42] and in vivo in animal models, including experimental autoimmune uveitis [43] and autoimmune diabetes [44]. Furthermore, selective blockade of galectin-1 in tumor tissue results in increased Th1-mediated anti-tumor responses, suggesting potential involvement of this protein in tumorimmune escape [45].…”

Novel role for galectin-1 in T-cells under physiological and pathological conditions

“…However the intracellular form of this protein has not been implicated in the process of apoptosis. Since Gal-1 has been proposed as a possible candidate for immunosuppressive therapy in earlier studies [8,11,13,33], we turned to the prototypical inflammatory autoimmune disease, SLE as a pathological model. Our results showed that active SLE T-cells contained significantly lower levels of Gal-1 mRNA than healthy controls.…”

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

“…Exogenous gal-1 has immunosuppressive and anti-inflammatory effects in experimental models of inflammation and autoimmunity such as inflammatory bowel disease, autoimmune retinal disease, autoimmune diabetes, and collagen-induced arthritis [5][6][7][8]. In addition, gal-1-deficient mice show augmented Th1 and Th17 responses and enhanced susceptibility to autoimmune neuroinflammation [3].…”