Research ArticleImmunology

Constrained TCRγδ-associated Syk activity engages PI3K to facilitate thymic development of IL-17A–secreting γδ T cells

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Science Signaling  20 Jul 2021:
Vol. 14, Issue 692, eabc5884
DOI: 10.1126/scisignal.abc5884

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A Goldilocks zone for γδ T cell development

T cells displaying the γδ form of the T cell receptor (TCRγδ) mediate responses to pathogens and have been implicated in autoimmune diseases. During their development in the thymus, γδ T cells can adopt an interleukin-17A–secreting fate (γδ17 cells) in response to weak TCRγδ signaling. Using an ex vivo mouse thymus culture system, Sumaria et al. found that low amounts of TCRγδ signaling stimulated similarly weak activation of the downstream kinase Syk, leading to PI3K-Akt signaling that was critical for the γδ17 fate. Increasing or decreasing the activity of this signaling axis inhibited the generation of γδ17 cells, demonstrating that the development of this subset of T cells is sensitive to TCR signal strength.

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