Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 214, Issue 9, Pages 2733-2758Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20161903
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Funding
- NHMRC of Australia [1013667, 1016701, 1047055]
- Cancer Council Victoria [1106291, 1106477]
- NHMRC [1020770, 1020363, 1103037]
- National Institutes of Health [R00-CA176376]
- Cuyamaca Foundation
- Bezos Family Foundation
- Deutsche Knochenmarkspenderdatei Foundation
- National Health and Medical Research Council of Australia [1103037] Funding Source: NHMRC
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In the thymus, hematopoietic progenitors commit to the T cell lineage and undergo sequential differentiation to generate diverse T cell subsets, including major histocompatibility complex (MHC)-restricted alpha beta T cell receptor (TCR) T cells and nonMHC- restricted gamma delta TCR T cells. The factors controlling precursor commitment and their subsequent maturation and specification into alpha beta TCR versus gamma delta TCR T cells remain unclear. Here, we show that the tyrosine phosphatase PTPN2 attenuates STAT5 (signal transducer and activator of transcription 5) signaling to regulate T cell lineage commitment and SRC family kinase LCK and STAT5 signaling to regulate alpha beta TCR versus gamma delta TCR T cell development. Our findings identify PTPN2 as an important regulator of critical checkpoints that dictate the commitment of multipotent precursors to the T cell lineage and their subsequent maturation into alpha beta TCR or gamma delta TCR T cells.
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