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Updated: Jul 11, 2026

Development of Stem Cell-derived Antigen-specific Regulatory T Cells Against Autoimmunity
Published on: November 8, 2016
PIP3 pathway in regulatory T cells and autoimmunity
Masaki Kashiwada1, Ping Lu, Paul B Rothman
1Division of Rheumatology, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Regulatory T cells (Tregs) play an important role in preventing both autoimmune and inflammatory diseases. Many recent studies have focused on defining the signal transduction pathways essential for the development and the function of Tregs. Increasing evidence suggest that T-cell receptor (TCR), interleukin-2 (IL-2) receptor (IL-2R), and co-stimulatory receptor signaling are important in the early development, peripheral homeostasis, and function of Tregs. The phosphoinositide-3 kinase (PI3K)-regulated pathway (PIP3 pathway) is one of the major signaling pathways activated upon TCR, IL-2R, and CD28 stimulation, leading to T-cell activation, proliferation, and cell survival. Activation of the PIP3 pathway is also negatively regulated by two phosphatidylinositol phosphatases SHIP and PTEN. Several mouse models deficient for the molecules involved in PIP3 pathway suggest that impairment of PIP3 signaling leads to dysregulation of immune responses and, in some cases, autoimmunity. This review will summarize the current understanding of the importance of the PIP3 pathway in T-cell signaling and the possible roles this pathway performs in the development and the function of Tregs.
Regulatory T cells (Tregs) play an important role in preventing both autoimmune and inflammatory diseases. Many recent studies have focused on defining the signal transduction pathways essential for the development and the function of Tregs. Increasing evidence suggest that T-cell receptor (TCR), interleukin-2 (IL-2) receptor (IL-2R), and co-stimulatory receptor signaling are important in the early development, peripheral homeostasis, and function of Tregs. The phosphoinositide-3 kinase (PI3K)-regulated pathway (PIP3 pathway) is one of the major signaling pathways activated upon TCR, IL-2R, and CD28 stimulation, leading to T-cell activation, proliferation, and cell survival. Activation of the PIP3 pathway is also negatively regulated by two phosphatidylinositol phosphatases SHIP and PTEN. Several mouse models deficient for the molecules involved in PIP3 pathway suggest that impairment of PIP3 signaling leads to dysregulation of immune responses and, in some cases, autoimmunity. This review will summarize the current understanding of the importance of the PIP3 pathway in T-cell signaling and the possible roles this pathway performs in the development and the function of Tregs.
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