AI Article Synopsis
- * Using single-cell RNA-sequencing, researchers discovered different pathways for developing thymocytes that respond to 5-OP-RU, including those selected by thymic epithelial cells and those influenced by bone-marrow-derived cells.
- * The study found that positive selection of MAIT cells depends on signaling through the SAP adapter, which regulates the transcription factor ZBTB16, thereby shaping the T cell lineage decisions during development.
Article Abstract
Mucosal-associated invariant T cells (MAIT cells) recognize the microbial metabolite 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU) presented by the MHC class Ib molecule, MR1. MAIT cells acquire effector functions during thymic development, but the mechanisms involved are unclear. Here we used single-cell RNA-sequencing to characterize the developmental path of 5-OP-RU-specific thymocytes. In addition to the known MAIT1 and MAIT17 effector subsets selected on bone-marrow-derived hematopoietic cells, we identified 5-OP-RU-specific thymocytes that were selected on thymic epithelial cells and differentiated into CD44 naive T cells. MAIT cell positive selection required signaling through the adapter, SAP, that controlled the expression of the transcription factor, ZBTB16. Pseudotemporal ordering of single cells revealed transcriptional trajectories of 5-OP-RU-specific thymocytes selected on either thymic epithelial cells or hematopoietic cells. The resulting model illustrates T cell lineage decisions.
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| http://dx.doi.org/10.1038/s41590-019-0465-3 | DOI Listing |
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