Role of phosphoinositide 3-kinase signaling in autoimmunity.
Activation of the phosphoinositide 3-kinase (PI3K) pathway promotes proliferation and survival in many different cell types of the immune system. PI3K acts downstream of receptors that mediate proliferation and survival in T cells, and required roles for individual class I PI3K catalytic isoforms have been established. Interestingly, mice with either augmented or diminished PI3K activity in T cells develop lymphoproliferation and signs of autoimmunity. Here, we summarize our current knowledge of mouse strains with hyperactive or reduced PI3K, different isoforms of class I PI3K in T cell-mediated immunity and autoimmunity, and the therapeutic implications for modulating this pathway for treatment of various autoimmune diseases.
Oak
Jean S
JS
Department of Molecular Biology and Biochemistry, Center for Immunology, University of California, Irvine, CA 92697, USA.
Fruman
David A
DA
D000818:Animals; D015551:Autoimmunity; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism
D048029:TNF Receptor-Associated Factor 6; D050721:Proto-Oncogene Proteins c-cbl; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C493849:Cbl protein, mouse