Cutting Edge: The Phosphoinositide 3-Kinase p110δ Is Critical for the Function of CD4+CD25+Foxp3+ Regulatory T Cells
Copyright policy )Cutting Edge: The Phosphoinositide 3-Kinase p110δ Is Critical for the Function of CD4+CD25+Foxp3+ Regulatory T Cells
Abstract CD4+CD25+Foxp3+ regulatory T cells (Tregs) contribute to the maintenance of peripheral tolerance by inhibiting the expansion and function of conventional T cells. Treg development and homeostasis are regulated by the Ag receptor, costimulatory receptors such as CD28 and CTLA-4, and cytokines such as IL-2, IL-10, and TGF-β. Here we show that the proportions of Tregs in the spleen and lymph nodes of mice with inactive p110δ PI3K (p110δD910A/D910A) are reduced despite enhanced Treg selection in the thymus. p110δD910A/D910A CD4+CD25+Foxp3+ Tregs showed attenuated suppressor function in vitro and failed to secrete IL-10. In adoptive transfer experiments, p110δD910A/D910A T cells failed to protect against experimental colitis. The identification of p110δ as an intracellular signaling protein that regulates the activity of CD4+CD25+Foxp3+ Tregs may facilitate the further elucidation of the molecular mechanisms responsible for Treg-mediated suppression.
- University College London United Kingdom
- University of Birmingham United Kingdom
- Ludwig Cancer Research United Kingdom
- Cellzome, GSK, Middlesex, UK.
- Royal Veterinary College United Kingdom
Inflammation, Mice, Knockout, Mice, Inbred BALB C, Class I Phosphatidylinositol 3-Kinases, Interleukin-2 Receptor alpha Subunit, Cell Differentiation, Forkhead Transcription Factors, T-Lymphocytes, Regulatory, Coculture Techniques, Growth Inhibitors, Mice, Mutant Strains, Interleukin-10, Mice, Inbred C57BL, Mice, Phosphatidylinositol 3-Kinases, Catalytic Domain, Animals, Interleukin-2, Cells, Cultured, Cell Proliferation
Inflammation, Mice, Knockout, Mice, Inbred BALB C, Class I Phosphatidylinositol 3-Kinases, Interleukin-2 Receptor alpha Subunit, Cell Differentiation, Forkhead Transcription Factors, T-Lymphocytes, Regulatory, Coculture Techniques, Growth Inhibitors, Mice, Mutant Strains, Interleukin-10, Mice, Inbred C57BL, Mice, Phosphatidylinositol 3-Kinases, Catalytic Domain, Animals, Interleukin-2, Cells, Cultured, Cell Proliferation
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