GALECTIN-1 SUPPRESSES AUTOIMMUNE RETINAL INFLAMMATION BY PROMOTING CONCOMITANT T HELPER-2- AND T REGULATORY--MEDIATED ANTI-INFLAMMATORY RESPONSES

MARTA A. TOSCANO; ALESSANDRA G. COMMODARO; JUAN M. ILARREGUI; GERMAN A. BIANCO; ANA LIBERMAN; HORACIO M. SERRA; JUN HIRABAYASHI; LUIZ V. RIZZO; GABRIEL A. RABINOVICH

JOURNAL OF IMMUNOLOGY

American Association of Immunologists

Lugar: Baltimore; Año: 2006 vol. 176 p. 6323 - 6332

0022-1767

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.