The methylation of the CTLA-4 promotor’s DNA at the NF-AT binding site resulted in insufficient CTLA-4 expression in RA patients’ Treg cells, which, in turn, leads to the failure of the expression and activation of the tryptophan degrading enzyme indoleamine 2,3-dioxygenase (IDO); as a consequence, the Treg cells were unable to activate the kynurenine pathway, which exacerbates the development of the RA (109). This evidence concerns the gene IDO1 and rheumatoid arthritis.