E2f2 Attenuates Apoptosis of Activated T Lymphocytes and Protects from Immune-Mediated Injury Through Repression of Fas and FasL

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Jan 11

PMID 35008734

Authors

Noor Mustafa

Jone Mitxelena

Arantza Infante

Olatz Zenarruzabeitia

Ainhoa Eriz

Ainhoa Iglesias-Ara

Ana M Zubiaga

Affiliations

Soon will be listed here.

Abstract

Targeted disruption of E2f2 in mice causes T-cell hyperactivation and a disproportionate cell cycle entry upon stimulation. However, mice do not develop a lymphoproliferative condition. We report that E2f2 plays a Fas-dependent anti-apoptotic function in vitro and in vivo. TCR-stimulated murine T cells overexpress the proapoptotic genes and and exhibit enhanced apoptosis, which is prevented by treatment with neutralizing anti-FasL antibodies. p53 pathway is activated in TCR-stimulated lymphocytes, but targeted disruption of p53 in mice does not abrogate Fas/FasL expression or apoptosis, implying a p53-independent apoptotic mechanism. We show that E2f2 is recruited to and gene promoters to repress their expression. in vivo, mice are prone to develop immune-mediated liver injury owing to an aberrant lymphoid Fas/FasL activation. Taken together, our results suggest that E2f2-dependent inhibition of Fas/FasL pathway may play a direct role in limiting the development of immune-mediated pathologies.

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