Interleukin-17-Producing γδ T Cells Originate from SOX13 Progenitors that Are Independent of γδTCR Signaling.
Spidale Nicholas A,Sylvia Katelyn,Narayan Kavitha,Miu Bing,Frascoli Michela,Melichar Heather J,Zhihao Wu,Kisielow Jan,Palin Amy,Serwold Thomas,Love Paul,Kobayashi Michihiro,Yoshimoto Momoko,Jain Nitya,Kang Joonsoo
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.