(The) immunosuppressive effect of Indolamine 2,3-dioxygenase (IDO) expressing neural stem cells in experimental autoimmune encephalomyelitis (EAE) animal model

Abstract

Neurodegenerative diseases provoke robust immunological reactions in the central nervous system, which deteriorate the neural tissue damage. In this study, primarily cultured rat fetal neural stem cells (NSCs) was engineered to express indoleamine 2,3-dioxygenase (IDO), an enzyme that has potent immune suppression activities. IDO expression would potentiate therapeutic effects of NSCs against neurodegenerative diseases, because NSCs could both prevent the secondary damage of neural tissues by immune reactions and regenerate damaged neural tissues. The immune suppressive effect of NSCs expressing IDO is validated by mixed leukocyte reaction (MLR) whereas the proliferation of lymphocytes was suppressed with NSC co-culture. In MLR, NSCs expressing IDO showed more suppressive feature compared to NSCs only. IDO inhibition using 1-Methyl-DL-Tryptophan (1-MT), IDO inhibitor, showed a decreased immune suppressive effect against T cell proliferation. Experimental autoimmune encephalomyelitis (EAE) results showed that the immune suppression effect was mediated by NSCs injection and more suppressive with NSCs expressing IDO. Taken together, NSCs expressing IDO synergistically suppressed immune response and is potentially suitable for development of therapeutic treatment against various neurodegenerative diseases.