PTPN2 regulates T cell lineage commitment and αß versus γδ specification
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2017-01-01
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Journal of Experimental Medicine (JEM)
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ROCKEFELLER UNIV PRESS
Melbourne Authors
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Microbiology and Immunology
Medical Biology (W.E.H.I.)
Sir Peter MacCallum Department of Oncology
Physiology
Medical Biology (W.E.H.I.)
Sir Peter MacCallum Department of Oncology
Physiology
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Journal Article
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Wiede, F., Dudakov, J. A., Lu, K. H., Dodd, G. T., Butt, T., Godfrey, D. I., Strasser, A., Boyd, R. L. & Tiganis, T. (2017). PTPN2 regulates T cell lineage commitment and αß versus γδ specification. Journal of Experimental Medicine, 214 (9), pp.2733-2758. https://doi.org/10.1084/jem.20161903.
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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 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 αβ TCR or γδ TCR T cells.