Interleukin-17-Producing γδ T Cells Originate from SOX13+ Progenitors that Are Independent of γδTCR Signaling.
Immunity
; 49(5): 857-872.e5, 2018 11 20.
Article
in En
| MEDLINE
| ID: mdl-30413363
ABSTRACT
Lineage-committed αß 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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Autoantigens
/
T-Lymphocytes
/
Signal Transduction
/
Receptors, Antigen, T-Cell, gamma-delta
/
Interleukin-17
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Year:
2018
Type:
Article