PTPN2 regulates T cell lineage commitment and αß versus γδ specification

Florian Wiede, Jarrod A. Dudakov, Kun-Hui Lu, Garron T. Dodd, Tariq Butt, Dale I. Godfrey, Andreas Strasser, Richard L. Boyd, Tony Tiganis

Research output: Contribution to journalArticleResearchpeer-review

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 languageEnglish
Pages (from-to)2733-2758
Number of pages26
JournalJournal of Experimental Medicine
Volume214
Issue number9
DOIs
Publication statusPublished - 4 Sep 2017

Cite this

Wiede, Florian ; Dudakov, Jarrod A. ; Lu, Kun-Hui ; Dodd, Garron T. ; Butt, Tariq ; Godfrey, Dale I. ; Strasser, Andreas ; Boyd, Richard L. ; Tiganis, Tony. / PTPN2 regulates T cell lineage commitment and αß versus γδ specification. In: Journal of Experimental Medicine. 2017 ; Vol. 214, No. 9. pp. 2733-2758.
@article{72bca0cada1f4943a64d2214bb9e6aba,
title = "PTPN2 regulates T cell lineage commitment and α{\ss} versus γδ specification",
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 α{\ss} 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 α{\ss} 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 α{\ss} 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 α{\ss} TCR or γδ TCR T cells.",
author = "Florian Wiede and Dudakov, {Jarrod A.} and Kun-Hui Lu and Dodd, {Garron T.} and Tariq Butt and Godfrey, {Dale I.} and Andreas Strasser and Boyd, {Richard L.} and Tony Tiganis",
year = "2017",
month = "9",
day = "4",
doi = "10.1084/jem.20161903",
language = "English",
volume = "214",
pages = "2733--2758",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "9",

}

Wiede, F, Dudakov, JA, Lu, K-H, Dodd, GT, Butt, T, Godfrey, DI, Strasser, A, Boyd, RL & Tiganis, T 2017, 'PTPN2 regulates T cell lineage commitment and αß versus γδ specification' Journal of Experimental Medicine, vol. 214, no. 9, pp. 2733-2758. https://doi.org/10.1084/jem.20161903

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 journalArticleResearchpeer-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

VL - 214

SP - 2733

EP - 2758

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 9

ER -