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Deletion of indoleamine 2,3 dioxygenase (Ido)1 but not Ido2 exacerbates disease symptoms of MOG35-55-induced experimental autoimmune encephalomyelitis

Wetzel, L;Hurtado, M;MacDowell Kaswan, Z;McCusker, R;Steelman, A;

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) with pathological features of inflammation, demyelination, and neurodegeneration. Several lines of evidence suggest that the enzymes indoleamine 2,3-dioxygenase (Ido)1 and/or Ido2 influences susceptibility to autoimmune diseases. Deletion of _Ido1_ exacerbates experimental autoimmune encephalomyelitis (EAE) an animal model of MS. However, no data exist on the role of _Ido2_ in the pathogenesis of EAE. We investigated whether deletion of _Ido2_ affected the pathogenesis of EAE. Temporal expression of interferon gamma (_Ifng_), _Ido1_ variants, _Ido2_ variants, as well as genes encoding enzymes of the kynurenine pathway in the spleen and spinal cord of C57BL/6 mice with or without EAE were determined by RT-qPCR. Moreover, EAE was induced in C57BL/6, two _Ido1_ knockout strains (Ido1KO and Ido1TK) and one Ido2 knockout mouse strain (Ido2?/?) and disease monitored by clinical scores and weight change. Performance on the rotarod was performed on days 0, 5, 10 and 15 post induction. The extent of demyelination in the spinal cord was determined after staining with Oil red O. The development of EAE altered gene expression in both the spleen and spinal cord. Deletion of _Ido1_ exacerbated the clinical symptoms of EAE. In stark contrast, EAE in Ido2?/? mice did not differ clinically or histologically from control mice. These results confirm a protective role for _Ido1_, on the pathogenesis of MOG35-55-induced EAE in C57BL/6J mice.