[PDF][PDF] Interleukin-17-producing γδ T cells originate from SOX13+ progenitors that are independent of γδTCR signaling

NA Spidale, K Sylvia, K Narayan, B Miu, M Frascoli… - Immunity, 2018 - cell.com
NA Spidale, K Sylvia, K Narayan, B Miu, M Frascoli, HJ Melichar, W Zhihao, J Kisielow…
Immunity, 2018cell.com
Lineage-committed αβ and γδ T cells are thought to originate from common intrathymic
multipotent progenitors following instructive T cell receptor (TCR) signals. A subset of lymph
node and mucosal Vγ2+ γδ T cells is programmed intrathymically to produce IL-17 (Tγδ17
cells), however the role of the γδTCR in development of these cells remains controversial.
Here we generated reporter mice for the Tγδ17 lineage-defining transcription factor SOX13
and identified fetal-origin, intrathymic Sox13+ progenitors. In organ culture developmental …
Summary
Lineage-committed αβ and γδ T cells are thought to originate from common intrathymic multipotent progenitors following instructive T cell receptor (TCR) signals. A subset of lymph node and mucosal Vγ2+ γδ T cells is programmed intrathymically to produce IL-17 (Tγδ17 cells), however the role of the γδTCR in development of these cells remains controversial. Here we generated reporter mice for the Tγδ17 lineage-defining transcription factor SOX13 and identified fetal-origin, intrathymic Sox13+ progenitors. In organ culture developmental assays, Tγδ17 cells derived primarily from Sox13+ progenitors, and not from other known lymphoid progenitors. Single cell transcriptome assays of the progenitors found in TCR-deficient mice demonstrated that Tγδ17 lineage programming was independent of γδTCR. Instead, generation of the lineage committed progenitors and Tγδ17 cells was controlled by TCF1 and SOX13. Thus, T lymphocyte lineage fate can be prewired cell-intrinsically and is not necessarily specified by clonal antigen receptor signals.
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