Endogenous galectin-9 potentiates CD4(+)T cell activation through promoting TCR downstream signaling

[[abstract]]Galectin-9, ab-galactoside-binding protein, is highly expressed in immune cells.Accumulating data indicated that galectin-9treatment induced T cell apoptosis and ameliorated autoimmune diseases in an exogenously modulated manner.However, endogenous role of galectin-9 in regulating T cells is largely unknown.We observed thatgalectin-9 is mostly expressed inside T cells and its membraneassociated and secreted forms are barely detected. Endogenous galectin-9 was quickly recruited to immune synapse upon T cell activation, suggesting its role in regulating TCR signaling. Our data revealed that proximal TCR signaling was impaired in galectin-9 deficient T cell, resulting in less proliferation through a Tim-3-independent pathway. Moreover, Th17 differentiation and B cell responses are downregulated in galectin-9 knockout mice. Finally, we demonstrated an inability of galectin-9 deficient T cells in the induction of T cell-transfer colitis and experimental autoimmune encephalomyelitis. Taken together, these findings indicate that intracellular galectin-9 is a positive regulator of T cell activation and modulates pathogenesis of autoimmune diseases