Indoleamine 2,3-dioxygenase (IDO1) is a heme protein that oxidizes the essential amino acid tryptophan to produce <i>N-</i>formylkynurenine. This enzyme is present in many tissues and is significantly upregulated in response to inflammation, specifically in the presence of cytokines such as IFNγ and bacterial lipopolysaccharides. Cells expressing IDO1 are able to deplete the inflamed environment of the metabolically expensive substrate, tryptophan, inhibiting the proliferation of immune targets. IDO1 also serves as an immunosuppressive enzyme. Cells expressing IDO1 inactivate surrounding immune cells through the combined effects of low tryptophan and high concentrations of kynurenine. T-cells are especially sensitive to low tryptophan concentrations, causing them to cease proliferation and to differentiate into immunosuppressive regulatory states. The importance of IDO1 in precise immune regulation is highlighted by its effects in a variety of processes and disease states including autoimmune disorders, response to infection, tolerance in transplantation, HIV infection, blood pressure regulation and the ability of cancer cells to avoid immune detection. In this lecture, we will discuss mechanisms by which human IDO1 affects the immune response.

Indoleamine 2,3-dioxygenase, the immune response and cancer

255th National Meeting (2018)

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