Journal article

PTPN2 regulates T cell lineage commitment and alpha beta versus gamma delta specification

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

JOURNAL OF EXPERIMENTAL MEDICINE | ROCKEFELLER UNIV PRESS | Published : 2017

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 αβ 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 αβ 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 αβ TCR versus γδ TCR T cell development. Our finding..

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Grants

Awarded by NHMRC of Australia


Awarded by Cancer Council Victoria


Awarded by NHMRC


Awarded by National Institutes of Health


Awarded by NATIONAL CANCER INSTITUTE


Funding Acknowledgements

This work was supported by the NHMRC of Australia (grant 1013667 to D.I. Godfrey, grant 1016701 to A. Strasser, and grant 1047055 to T. Tiganis) and the Cancer Council Victoria (grant 1106291 to A. Strasser and grant 1106477 to F. Wiede). D.I. Godfrey and A. Strasser are NHMRC Senior Principal Research Fellows (grants 1020770 and 1020363, respectively), and T. Tiganis is an NHMRC Principal Research Fellow (grant 1103037). J.A. Dudakov was supported by the National Institutes of Health (grant R00-CA176376), the Cuyamaca Foundation, the Bezos Family Foundation, and the Mechtild Harf Award from the Deutsche Knochenmarkspenderdatei Foundation for Giving Life.