The critical role of methylenetetrahydrofolate dehydrogenases in immune regulation and auto-immunity.

1-carbon (1 C) metabolism is a key process required for nucleotide synthesis in activated lymphocytes and other immune-regulatory mechanisms. Commonly used and well-established drugs for the treatment of inflammatory disorders such as methotrexate and fluorouracil (5-FU) are known to interact with 1 C metabolism And provide appreciable clinical benefit despite challenges with tolerance And patient compliance. Advances in our understanding of the enzymes involved in 1 C metabolism coupled with differential expression highlights specific targeting of key enzymes may greatly enhance clinical efficacy And reduce side effect burden in comparison to the established therapies that are more indiscriminate in their mode of action. In recent years the methylenetetrahydrofolate dehydrogenase enzymes have gained increasing interest because of the role they play in 1 C metabolism in the immune system and in progression of inflammatory diseases. High expression of these enzymes in activated immune cells and inflamed tissues coupled with chemical tractability provides compelling reasons to actively consider these enzymes as novel therapeutic targets.