RT Journal Article
T1 Class IB phosphatidylinositol 3-kinase (PI3K) deficiency ameliorates IA-PIK-induced systemic lupus but not T cell invasion
A1 Barber, Domingo F.
A1 Bartolomé, Almira
A1 Hernández, Carmen
A1 Flores Landeira, Juana María
A1 Fernández Arias, Cristina
A1 Rodríguez Borlado, Luis
A1 Hirsch, Emilio
A1 Wymann, Matthias
A1 Balomenos, Dimitrios
A1 Carrera, Ana C.
AB Class 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.
PB American Association of Immunologists
SN 1550-6606
YR 2006
FD 2006-01-01
LK https://hdl.handle.net/20.500.14352/96118
UL https://hdl.handle.net/20.500.14352/96118
LA eng
NO Barber 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.
NO Unión Europea
NO Comunidad Autónoma de Madrid
NO Fundación Ramón Areces
NO Dirección General de Ciencia y Desarrollo Tecnológico
DS Docta Complutense
RD 8 abr 2025