Bosque, AlbertoAguiló, Juan IgnacioAlava, M. AngelesNaval, JavierAnel, AlbertoPaz Artal, Estela NatividadAllende Martínez, Luis Miguel2024-02-022024-02-022006-10-24Bosque A, Aguiló JI, Alava MA, Paz-Artal E, Naval J, Allende LM, Anel A. The induction of Bim expression in human T-cell blasts is dependent on nonapoptotic Fas/CD95 signaling. Blood. 2007 Feb 15;109(4):1627-35. doi: 10.1182/blood-2006-05-022319. Epub 2006 Oct 24. PMID: 17062728.0006-49711528-002010.1182/blood-2006-05-022319https://hdl.handle.net/20.500.14352/98440The BH3-only protein Bim is required for maintaining the homeostasis of the immune system, since Bim regulates the down-modulation of T-cell responses, mainly through cytokine deprivation. Using T-cell blasts from healthy donors and also from patients with autoimmune lymphoproliferative syndromes (ALPSs) due to homozygous loss-of-function mutation of FasL (ALPS-Ic) or heterozygous mutation in the Fas/CD95 death domain (ALPS-Ia), it is shown that the induction of Bim expression during the process of human T-cell blast generation is strictly dependent on FasL/Fas-mediated signaling. The main pathway by which Fas signaling regulates the levels of Bim expression in human T-cell blasts is the death-domain- and caspase-independent generation of discrete levels of H2O2, which results in the net increase of Foxo3a levels. The present results connect the 2 main pathways described until the moment for the control of T-cell responses: death receptor-mediated activation-induced cell death and apoptosis by cytokine deprivation.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal articlehttps://www.sciencedirect.com/science/article/pii/S0006497120420063?via%3Dihubopen access636.9.09:616.15Ciencias Biomédicas32 Ciencias Médicas