PTPN2 regulates T cell lineage commitment and αβ versus γδ specification

F Wiede, JA Dudakov, KH Lu, GT Dodd, T Butt… - Journal of Experimental …, 2017 - rupress.org
F Wiede, JA Dudakov, KH Lu, GT Dodd, T Butt, DI Godfrey, A Strasser, RL Boyd, T Tiganis
Journal of Experimental Medicine, 2017rupress.org
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 …
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.
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