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

International Journal of Molecular Sciences

Noor Mustafa¹  Jone Mitxelena¹  Ainhoa Eriz¹  Ana M. Zubiaga¹  Ainhoa Iglesias-Ara¹  Olatz Zenarruzabeitia²  Arantza Infante³ 

[1] Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country, UPV/EHU, 48080 Bilbao, Spain;Immunopathology Group, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain;Stem Cells and Cell Therapy Laboratory, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain;

关键词: E2f;    apoptosis;    Fas;    FasL;    T lymphocytes;    immune disorder;   

DOI  :  10.3390/ijms23010311

来源: DOAJ

【 摘 要 】

Targeted disruption of E2f2 in mice causes T-cell hyperactivation and a disproportionate cell cycle entry upon stimulation. However, E2f2^−/− 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 E2f2^−/− T cells overexpress the proapoptotic genes Fas and FasL and exhibit enhanced apoptosis, which is prevented by treatment with neutralizing anti-FasL antibodies. p53 pathway is activated in TCR-stimulated E2f2^−/− lymphocytes, but targeted disruption of p53 in E2f2^−/− mice does not abrogate Fas/FasL expression or apoptosis, implying a p53-independent apoptotic mechanism. We show that E2f2 is recruited to Fas and FasL gene promoters to repress their expression. in vivo, E2f2^−/− 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.

【 授权许可】

Unknown