Barber, Domingo F.Bartolomé, AlmiraHernández, CarmenFlores Landeira, Juana MaríaFernández Arias, CristinaRodríguez Borlado, LuisHirsch, EmilioWymann, MatthiasBalomenos, DimitriosCarrera, Ana C.2024-01-292024-01-292006-01-01Barber DF, Bartolomé A, Hernandez C, Flores JM, Fernandez-Arias C, Rodríguez-Borlado L, Hirsch E, Wymann M, Balomenos D, Carrera AC. Class IB-phosphatidylinositol 3-kinase (PI3K) deficiency ameliorates IA-PI3K-induced systemic lupus but not T cell invasion. J Immunol. 2006 Jan 1;176(1):589-93. doi: 10.4049/jimmunol.176.1.589. PMID: 16365454.1550-660610.4049/jimmunol.176.1.589https://hdl.handle.net/20.500.14352/96118Class I PI3K catalyzes formation of 3-poly-phosphoinositides. The family is divided into IA isoforms, activated by Tyr kinases and the IB isoform (PI3Kγ), activated by G protein-coupled receptors. Mutations that affect PI3K are implicated in chronic inflammation, although the differential contribution of each isoform to pathology has not been elucidated. Enhanced activation of class IA-PI3K in T cells extends CD4+ memory cell survival, triggering an invasive lymphoproliferative disorder and systemic lupus. As both IA- and IB-PI3K isoforms regulate T cell activation, and activated pathogenic CD4+ memory cells are involved in triggering systemic lupus, we examined whether deletion of IB could reduce the pathological consequences of increased IA-PI3K activity. IB-PI3Kγ deficiency did not abolish invasion or lymphoproliferation, but reduced CD4+ memory cell survival, autoantibody production, glomerulonephritis, and systemic lupus. Deletion of the IB-PI3Kγ isoform thus decreased survival of pathogenic CD4+ memory cells, selectively inhibiting systemic lupus development. These results validate the PI3Kγ isoform as a target for systemic lupus erythematosus treatment.engjournal articlehttps://journals.aai.org/jimmunol/article/176/1/589/75251/Class-IB-Phosphatidylinositol-3-Kinase-PI3Khttps://pubmed.ncbi.nlm.nih.gov/16365454/open access612.017Biología24 Ciencias de la Vida2412 Inmunología