Similarly, the metabolic by-products of tryptophan, such as kynurenine, triggers iTreg proliferation by its binding to the aryl hydrocarbon receptor [71, 72]. However, iTregs in the absence of tryptophan can activate the amino-acid-starvation sensor GCN2 (general control nonderepressible-2) kinase that inhibits Th17 cell differentiation [73, 74] and supports Treg stability. It has been reported that Tregs upregulate amino-acid-consuming enzymes including ARG1 (arginase 1), HDC (histidine decarboxylase), TDH (threonine dehydrogenase), and IL4I1 (interleukin-4 induced 1) in skin graft as compared to fresh skin to induce tolerance. These findings suggest that Tregs can modulate the concentration of essential amino acids and their catabolic products in the intrinsic cell milieu through the activation of amino acid starvation sensors [75]. In this way, Tregs trigger suppression through amino acid starvation and limit the pathology during the normal immune response.