MRNA-delivery of IDO1 suppresses T cell-mediated autoimmunity.

ABSTRACT: Indoleamine-2,3-dioxygenase (IDO)1 degrades tryptophan, obtained through dietary intake, into immunoregulatory metabolites of the kynurenine pathway. Deficiency or blockade of IDO1 results in the enhancement of autoimmune severity in rodent models and increased susceptibility to developing autoimmunity in humans. Despite this, therapeutic modalities that leverage IDO1 for the treatment of autoimmunity remain limited. Here, we use messenger (m)RNA formulated in lipid nanoparticles (LNPs) to deliver a human IDO1 variant containing the myristoylation site of Src to anchor the protein to the inner face of the plasma membrane. This membrane-anchored IDO1 has increased protein production, leading to increased metabolite changes, and ultimately ameliorates disease in three models of T cell-mediat

SUBMITTER: Kenney LL 

PROVIDER: S-EPMC11525033 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature