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αβ/γδ T cell lineage outcome is regulated by intrathymic cell localization and environmental signals.

Narges AghaallaeiAdvaita M DickErika TsingosDaigo InoueEva HaselThomas ThumbergerAtsushi ToyodaMaria LeptinJoachim WittbrodtBaubak Bajoghli
Published in: Science advances (2021)
αβ and γδ T cells are two distinct sublineages that develop in the vertebrate thymus. Thus far, their differentiation from a common progenitor is mostly understood to be regulated by intrinsic mechanisms. However, the proportion of αβ/γδ T cells varies in different vertebrate taxa. How this process is regulated in species that tend to produce a high frequency of γδ T cells is unstudied. Using an in vivo teleost model, the medaka, we report that progenitors first enter a thymic niche where their development into γδ T cells is favored. Translocation from this niche, mediated by chemokine receptor Ccr9b, is a prerequisite for their differentiation into αβ T cells. On the other hand, the thymic niche also generates opposing gradients of the cytokine interleukin-7 and chemokine Ccl25a, and, together, they influence the lineage outcome. We propose a previously unknown mechanism that determines the proportion of αβ/γδ lineages within species.
Keyphrases
  • high frequency
  • single cell
  • transcranial magnetic stimulation
  • cell fate
  • transcription factor
  • cell therapy
  • dendritic cells
  • genetic diversity
  • regulatory t cells
  • liver fibrosis
  • bone marrow
  • climate change