Indolamine 2,3‐dioxygenase is expressed in the CNS and down‐regulates autoimmune inflammation

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Abstract
SPECIFIC AIMSThe mechanisms of spontaneous recovery from autoimmune central nervous system (CNS) inflammation in multiple sclerosis (MS) and its animal model autoimmune encephalomyelitis (EAE) remain poorly understood. One requirement for recovery from EAE is the control over self-reactive T cells from the CNS and the periphery. The tryptophan (trp)-degrading enzyme IDO is the first and rate-limiting enzyme of the kynurenine pathway. IDO activation reduces T cell proliferation and susceptibility to CD95L-induced apoptosis due to tryptophan depletion and the production of T cell-toxic tryptophan metabolites such as 3-hydrocyanthranilic acid and quinolic acid.Therefore, the primary aim of our work was to determine whether IDO is expressed and active within the CNS during autoimmune inflammation in EAE-induced SJL mice. To assess time-dependent IDO activity in the relapsing-remitting disease course, we analyzed the relative IDO activity within the CNS and spleen by HPLC. The clinical relevance of IDO express...
Funding Information
  • California Department of Fish and Game (2272/1‐2)