Directing T cell differentiation and function with small molecule inhibitors.
Regulatory T (Treg) cells that express the signature transcription factor Foxp3 safeguard against autoimmunity and immune pathology. Recent studies show that a signaling network with the components phosphatidyl inositol 3 kinase (PI3K), Akt, and the mammalian target of rapamycin (mTOR) regulates the de novo expression of Foxp3 in CD4 T cells. In addition to CD4 T cell differentiation, PI3K/Akt/mTOR signaling also controls T cell migration. Here we review the new data, consider their evolutionary context and discuss their potential implications for immunotherapy.
Bruno
Ludovica
L
Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom.
Merkenschlager
Matthias
M
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D005502:Food; D005786:Gene Expression Regulation / Q000502:physiology; D006131:Growth Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods / Q000639:trends; D008954:Models, Biological; D051058:Oncogene Protein v-akt / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases
D006131:Growth Inhibitors; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D011948:Receptors, Antigen, T-Cell; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human