The PI3K/Akt/mTOR pathway in innate immune cells: emerging therapeutic applications.
The phosphatidylinositol-3 kinases (PI3Ks) and the mammalian target of rapamycin (mTOR) pathway have long been recognised as critically regulating metabolism, growth or survival. Recent data indicate that these molecules are also integral players in coordinating defence mechanisms in the innate immune system. In this respect, PI3K and mTOR positively regulate immune cell activation in neutrophils and mast cells. In plasmacytoid dendritic cells, these pathways have recently emerged as important regulators for type I interferon production via activation of the interferon-regulatory factor 7. Interestingly, in myeloid immune cells, PI3K and mTOR seem to constrain full immune cell activation by upregulation of the key anti-inflammatory cytokine interleukin 10 and inhibition of proinflammatory cytokines. These new insights into innate immune cell regulation may pave the way for manipulating distinct features of the innate immune system for therapeutic treatment of various inflammatory diseases and for implementation of improved vaccination strategies.
Weichhart
T
T
Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University Vienna, Vienna, Austria.
Säemann
M D
MD
D003713:Dendritic Cells / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008407:Mast Cells / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011494:Protein Kinases / Q000276:immunology*; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D058570:TOR Serine-Threonine Kinases
D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human