[초청강연] T cell survival and autoimmune disease

AbstractRelapses and disease exacerbations are vexing features of multiplesclerosis. Osteopontin (Opn), which is expressed in multiple sclerosislesions, is increased in patients` plasma during relapses. Here, inmodels of multiple sclerosis including relapsing, progressive andmultifocal experimental autoimmune encephalomyelitis (EAE), Opntriggered recurrent relapses, promoted worsening paralysis and inducedneurological deficits, including optic neuritis. Increasedinflammation followed Opn administration, whereas its absence resultedin more cell death of brain-infiltrating lymphocytes. Opn promoted thesurvival of activated T cells by inhibiting the transcription factorFoxo3a, by activating the transcription factor NF-B through inductionof phosphorylation of the kinase IKK and by altering expression of theproapoptotic proteins Bim, Bak and Bax. Those mechanisms collectivelysuppressed the death of myelin-reactive T cells, linking Opn to therelapses and insidious progression characterizing multiple sclerosis.