Roles of Galectin-9 in the Development of Experimental Allergic Conjunctivitis in Mice

<i>Background:</i> Galectin-9 was recently identified as a ligand for Tim-3, which negatively regulates Th1 cells. Here, we investigated whether administration of anti-galectin-9 antibodies (Abs) affects the development of murine experimental allergic conjunctivitis (EC), a Th2-mediated disease. <i>Methods:</i> EC was induced in BALB/c mice by active immunization with ragweed (RW) followed by RW challenge in eye drops. Normal rat IgG (nrIgG) or anti-galectin-9 Ab was injected intraperitoneally into the mice either during the induction phase treatment or effector phase treatment. Alternatively, Abs were injected into the subconjunctival space during the effector phase. To evaluate in vitro effects of anti-galectin-9 Abs, splenocytes from RW-sensitized mice were cultured in vitro with RW in the presence of nrIgG or anti-galectin-9 Abs. To induce EC, these splenocytes were transferred into naïve BALB/c mice followed by RW challenge. <i>Results:</i> Treatment with anti-galectin-9 Abs in vivo during either the induction or effector phase did not significantly affect the severity of EC. However, when the splenocytes from RW-primed mice treated with anti-galectin-9 Abs during the induction phase were stimulated in vitro and adoptively transferred into naïve recipients, they induced significantly severer EC. In contrast, when RW-primed splenocytes were restimulated in vitro with RW in the presence of anti-galectin-9 Abs and then adoptively transferred, they induced less severe EC and produced significantly less IL-5 and IL-13 and more IFN-γ compared to nrIgG-treated control splenocytes. <i>Conclusions:</i> These observations may reflect the fact that galectin-9 not only regulates T-cell function, it is also involved in many other biological functions.