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

14 Citations (Scopus)

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