Research ArticleTHYMUS

Metabolic signaling directs the reciprocal lineage decisions of αβ and γδ T cells

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Science Immunology  06 Jul 2018:
Vol. 3, Issue 25, eaas9818
DOI: 10.1126/sciimmunol.aas9818

Wiring metabolic signaling circuits in thymocytes

Cell differentiation is often accompanied by metabolic changes. Yang et al. report that generation of double-positive (DP) thymocytes from double-negative (DN) cells coincides with dynamic regulation of glycolytic and oxidative metabolism. Given the central role of mechanistic target of rapamycin complex 1 (mTORC1) signaling in regulating metabolic changes, they examined the role of mTORC1 pathway in thymocyte development by conditionally deleting RAPTOR, the key component of the mTORC1 complex, in thymocytes. Loss of RAPTOR impaired the DN-to-DP transition, but unexpectedly also perturbed the balance between αβ and γδ T cells and promoted the generation of γδ T cells. Their studies highlight an unappreciated role for mTORC1-dependent metabolic changes in controlling thymocyte fates.

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