Institute of Developmental Biology and Molecular Medicine

Shanghai, China

Institute of Developmental Biology and Molecular Medicine

Shanghai, China
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Ye J.,Institute of Developmental Biology and Molecular Medicine | Shi H.,Institute of Developmental Biology and Molecular Medicine | Shen Y.,Institute of Developmental Biology and Molecular Medicine | Peng C.,Institute of Developmental Biology and Molecular Medicine | And 10 more authors.
Journal of Immunology | Year: 2015

T cell development and homeostasis are both regulated by TCR signals. Protein phosphorylation and dephosphorylation, which are catalyzed by protein kinases and phosphatases, respectively, serve as important switches controlling multiple downstream pathways triggered by TCR recognition of Ags. It has been well documented that protein tyrosine phosphatases are involved in negative regulation of proximal TCR signaling. However, how TCR signals are terminated or attenuated in the distal TCR signaling pathways is largely unknown. We investigated the function of Ser/Thr protein phosphatase (PP) 6 in TCR signaling. T cell lineage-specific ablation of PP6 in mice resulted in enhanced thymic positive and negative selection, and preferential expansion of fetal-derived, IL-17-producing Vγ6Vd1+ T cells. Both PP6-deficient peripheral CD4+ helper and CD8+ cytolytic cells could not maintain a naive state and became fast-proliferating and short-lived effector cells. PP6 deficiency led to profound hyperactivation of multiple distal TCR signaling molecules, including MAPKs, AKT, and NF-κB. Our studies demonstrate that PP6 acts as a critical negative regulator, not only controlling both αβ and γδ lineage development, but also maintaining naive T cell homeostasis by preventing their premature activation before Ag stimulation. Copyright © 2015 by The American Association of Immunologists, Inc.


Li R.,Institute of Developmental Biology and Molecular Medicine | Zhuang Y.,Institute of Developmental Biology and Molecular Medicine | Zhuang Y.,Duke University | Han M.,Institute of Developmental Biology and Molecular Medicine | And 4 more authors.
DMM Disease Models and Mechanisms | Year: 2013

The stable genomic integration and expression of a large transgene is a major hurdle in gene therapy. We show that the modified piggyBac (PB) transposon system can be used to introduce a 207 kb genomic DNA fragment containing the RORγ/γt locus into human cells and mice. PB-mediated transgenesis results in a single copy of a stably inherited and expressed transgene. These results indicate that PB could serve as an effective high-capacity vector for functional analysis of the mammalian genome and for gene therapy in human cells. © 2013. Published by The Company of Biologists Ltd.

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