Galectin–1 Suppresses Autoimmune Retinal Disease by Promoting Th2–Mediated Anti–Inflammatory Responses

L. RIZZO; A.G. COMMODARO; M.A. TOSCANO; G.A. RABINOVICH

Florida, USA

Congreso; ARVO 2006; 2006

ARVO

Galectin–1 Suppresses Autoimmune Retinal Disease by Promoting Th2–Mediated Anti–Inflammatory Responses L.V. Rizzo1, A.G. Commodaro1, M. Toscano2 and G. Rabinovich2 1 Immunology, University of São Paulo, São Paulo, Brazil2 Immunology, University Buenos Aires, Buenos Aires, Argentina Commercial Relationships: L.V. Rizzo, None; A.G. Commodaro, None; M. Toscano, None; G. Rabinovich, None. Support: CNPq, FAPESP, CAPES Abstract Purpose: Intraocular inflammatory diseases are a common cause of visual impairment and blindness. Here we explored 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 T–helper (Th)–1–mediated model of ocular disease. Methods: B10.RIII mice were immunized s.c. with 50µg of IRBP emulsified in CFA, plus 0,4µg of Bordetella pertussis toxin in 0,1ml i.p. as an additional adjuvant. Animals were treated or not with 50µg of Gal–1 i.p. in the afferent phase of disease (2, 4 and 6 days post immunization–dpi) or in the efferent phase (14, 16 and 18 dpi). Lymph nodes were collected 21 days after immunization and cells were cultured to evaluate the apoptosis analysis and determine cytokine synthesis. Disease severity was evaluated by histological examination of the eyes enucleated at day 21. Results: Treatment with Gal–1 was sufficient to suppress ocular pathology. Interestingly, administration of Gal–1 at the afferent phase of EAU resulted in a dramatic decrease in IFN– production and a marked increase in IL–5 and IL–10 secretion by lymph node cells. This effect was accompanied by a substantial increase in GATA3 levels at days 4 and 6 following Gal–1 treatment. Thus, treatment with Gal–1 at early phases of EAU was sufficient to shift the uveitogenic response towards a non–pathogenic Th2 profile. Gal–1 in this particular model did not result in significant levels of immune cell apoptosis, suggesting that Gal–1 may also exert its immunoregulatory activity through alternative anti–inflammatory pathways. Conclusions: These results are indicative of the possible therapeutic use of Gal–1 in autoimmune processes. Key Words: autoimmune disease • inflammation • uveitis-clinical/animal model