4.7 Article

PTPN2 regulates T cell lineage commitment and αβ versus γδ specification

期刊

JOURNAL OF EXPERIMENTAL MEDICINE
卷 214, 期 9, 页码 2733-2758

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ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20161903

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资金

  1. NHMRC of Australia [1013667, 1016701, 1047055]
  2. Cancer Council Victoria [1106291, 1106477]
  3. NHMRC [1020770, 1020363, 1103037]
  4. National Institutes of Health [R00-CA176376]
  5. Cuyamaca Foundation
  6. Bezos Family Foundation
  7. Deutsche Knochenmarkspenderdatei Foundation
  8. National Health and Medical Research Council of Australia [1103037] Funding Source: NHMRC

向作者/读者索取更多资源

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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