MAIT cell development in mice. 5-A-RU-derived MAIT ligands, mostly produced in the colon mucosa, travel to the thymus and contribute to the positive selection and/or intrathymic expansion of MAIT cells, in particular the MAIT17 subset. Upon positive selection by CD4⁺CD8⁺ DP thymocytes, MAIT cell precursors express PLZF and differentiate into either MAIT1 or MAIT17 cells. Expression of distinct homing proteins in each subset targets MAIT1 cells preferentially to the spleen and liver, while MAIT17 cells are home to barrier tissues such as lung, skin, and gut lamina propria. In addition to 5-A-RU-derived ligands, a bile acid metabolite primarily produced by bacterial bile salt hydrolases (BSH) can also be found in the thymus and modulate MAIT cell development. Created with Biorender.