Wiede Florian, Dudakov Jarrod A, Lu Kun-Hui, Dodd Garron T, Butt Tariq, Godfrey Dale I, Strasser Andreas, Boyd Richard L, Tiganis Tony
Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
J Exp Med. 2017 Sep 4;214(9):2733-2758. doi: 10.1084/jem.20161903. Epub 2017 Aug 10.
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.
在胸腺中，造血祖细胞定向分化为T细胞谱系，并经历一系列分化过程，以产生多种T细胞亚群，包括主要组织相容性复合体（MHC）限制性αβT细胞受体（TCR）T细胞和非MHC限制性γδTCR T细胞。控制前体细胞定向分化以及随后成熟并分化为αβTCR或γδTCR T细胞的因素仍不清楚。在此，我们表明酪氨酸磷酸酶PTPN2减弱STAT5（信号转导子和转录激活子5）信号传导，以调节T细胞谱系定向分化，并且减弱SRC家族激酶LCK和STAT5信号传导，以调节αβTCR与γδTCR T细胞的发育。我们的研究结果确定PTPN2是关键检查点的重要调节因子，这些检查点决定了多能前体细胞向T细胞谱系的定向分化以及随后成熟为αβTCR或γδTCR T细胞的过程。
Zotero 插件
