Abstract
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 αß T cell receptor (TCR ) T cells and non- MHC-restricted γδ TCR T cells. The factors controlling precursor commitment and their subsequent maturation and specification into αß TCR versus γδ 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 αß TCR versus γδ 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 αß TCR or γδ TCR T cells.
| Original language | English |
|---|---|
| Pages (from-to) | 2733-2758 |
| Number of pages | 26 |
| Journal | Journal of Experimental Medicine |
| Volume | 214 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 4 Sep 2017 |
Cite this
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PTPN2 regulates T cell lineage commitment and αß versus γδ specification. / Wiede, Florian; Dudakov, Jarrod A.; Lu, Kun-Hui; Dodd, Garron T.; Butt, Tariq; Godfrey, Dale I.; Strasser, Andreas; Boyd, Richard L.; Tiganis, Tony.
In: Journal of Experimental Medicine, Vol. 214, No. 9, 04.09.2017, p. 2733-2758.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - PTPN2 regulates T cell lineage commitment and αß versus γδ specification
AU - Wiede, Florian
AU - Dudakov, Jarrod A.
AU - Lu, Kun-Hui
AU - Dodd, Garron T.
AU - Butt, Tariq
AU - Godfrey, Dale I.
AU - Strasser, Andreas
AU - Boyd, Richard L.
AU - Tiganis, Tony
PY - 2017/9/4
Y1 - 2017/9/4
N2 - 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 αß T cell receptor (TCR ) T cells and non- MHC-restricted γδ TCR T cells. The factors controlling precursor commitment and their subsequent maturation and specification into αß TCR versus γδ 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 αß TCR versus γδ 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 αß TCR or γδ TCR T cells.
AB - 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 αß T cell receptor (TCR ) T cells and non- MHC-restricted γδ TCR T cells. The factors controlling precursor commitment and their subsequent maturation and specification into αß TCR versus γδ 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 αß TCR versus γδ 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 αß TCR or γδ TCR T cells.
UR - http://www.scopus.com/inward/record.url?scp=85028862426&partnerID=8YFLogxK
U2 - 10.1084/jem.20161903
DO - 10.1084/jem.20161903
M3 - Article
AN - SCOPUS:85028862426
VL - 214
SP - 2733
EP - 2758
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 9
ER -