Jianrong Li
Texas A&M University, USA
Title: Galectin-9 modulates inflammatory demyelination and myelin repair
Biography
Biography: Jianrong Li
Abstract
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Local inflammatory reactions induced by infiltrating leukocytes and activated glia are believed to be the main culprit for myelin destruction and axonal damage. Recent studies suggest that galectins, the ß-galactoside-binding lectins, can modulate immune tolerance and inflammatory responses. Galectin-9 is significantly elevated in MS lesions, however, its function in CNS immune responses and demyelination remains largely unexplored. We found that galectin-9 was markedly induced in microglia and reactive astrocytes during experimental autoimmune encephalomyelitis (EAE), an animal model of MS, as well as in reactive astrocytes and microglia/macrophages surrounding active MS lesions. Pro-inflammatory cytokines such as TNF and IL-1b triggered galectin-9 production from astrocytes, which in turn acted in a feed-forward fashion to further enhance microglial TNF production. TNF-stimulated Lgals9+/+ astrocytes induced greater extent of encephalitogenic T-cell apoptosis and proliferation arrest than that of Lgals9-/- astrocytes, indicating that galectin-9 negatively regulates encephalitogenic T cells. During MOG35-55-induced EAE, Lgals9-/- mice exhibited worse clinical symptoms, which were associated with heightened Th17 responses in the CNS and demyelination when compared with littermate Lgals9+/+ controls. In autoimmunity-independent toxin models of CNS demyelination, spontaneous remyelination was delayed in Lgals9-/- mice. Immunohistochemistry analyses revealed that although Lgals9-/- mice had similar number of oligodendrocyte precursor cells in the lesions as control mice, the number of mature oligodendrocytes was significantly reduced. Consistently, recombinant galectin-9 promoted oligodendrocyte maturation in mixed glial cultures. Collectively, our data suggest a role for galectin-9 in suppressing T lymphocytes in the CNS and facilitating oligodendrocyte maturation and myelin repair