MAIT cells egress the thymus at several maturation stages with selective capacity to seed different tissues.

Mucosal-associated invariant T (MAIT) and invariant natural killer T (iNKT) cells participate in tissue homeostasis and repair and in defense against pathogens. While MAIT and iNKT cells share a developmental pathway leading to the expression of effector-memory and tissue-residency programs, differences in subset proportions and tissue distribution suggest lineage-specific developmental mechanisms. We show that thymic epithelial cells contribute to MAIT but not to iNKT cell selection, which relies solely on double-positive thymocytes. Nonetheless, MAIT and iNKT cells had similar developmental kinetics and thymic residency properties. MAIT cells egressed the thymus at several developmental stages and colonized specific tissues. Semi-mature cells seeded the intestine via chemokine receptor CCR9. Thymic output during adulthood contributed to tissue MAIT and iNKT cell homeostasis. Lastly, MAIT ligands produced during colitis induced thymic MAIT17 cell expansion and migration to the colon, which suggests a feedback loop that boosts the production of MAIT cells capable of re-establishing epithelial integrity.