During fetal development, transient waves of progenitors arise and generate distinct immune cells that persist and contribute to the mature immune system. Elsaid et al elegantly demonstrate that 2 distinct waves of ETPs arise from HSC-derived progenitors and differentially contribute to thymic innate-immune cell establishment and mTEC maturation. Blockade of the first, but not the second, wave of ETPs by anti-IL7Rα injection results in significantly less thymic LTi cells, Vγ5+ γδ T cells, and mature mTECs. These results were recapitulated in neonates after complete thymectomy. Altogether, these data suggest that the initial wave of ETPs specifically contributes to the establishment of innate-immune cell compartments in the developing thymus and is required for the maturation of AIRE-expressing mTECs. AGM, aorta-gonad-mesonephros; dHSC, definitive HSC; drHSC, developmentally-restricted HSC; EMP, erythro-myeloid progenitor; GM, granulocyte/monocyte; pHSC, primitive HSC.

During fetal development, transient waves of progenitors arise and generate distinct immune cells that persist and contribute to the mature immune system. Elsaid et al elegantly demonstrate that 2 distinct waves of ETPs arise from HSC-derived progenitors and differentially contribute to thymic innate-immune cell establishment and mTEC maturation. Blockade of the first, but not the second, wave of ETPs by anti-IL7Rα injection results in significantly less thymic LTi cells, Vγ5+ γδ T cells, and mature mTECs. These results were recapitulated in neonates after complete thymectomy. Altogether, these data suggest that the initial wave of ETPs specifically contributes to the establishment of innate-immune cell compartments in the developing thymus and is required for the maturation of AIRE-expressing mTECs. AGM, aorta-gonad-mesonephros; dHSC, definitive HSC; drHSC, developmentally-restricted HSC; EMP, erythro-myeloid progenitor; GM, granulocyte/monocyte; pHSC, primitive HSC.

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