STING modulates necrotic cell death in CD4 T cells via activation of PARP-1/PAR following acute systemic inflammation.
Int Immunopharmacol
; 109: 108809, 2022 Aug.
Article
em En
| MEDLINE
| ID: mdl-35504207
ABSTRACT
Regulated cell death profoundly affects on the progress of inflammatory and immune responses in various acute inflammatory diseases, as seen in sepsis and trauma. However, the mechanisms underlying CD4 T cells death have not yet been fully addressed. We demonstrated that interferon genes (STING) promoted excessive Poly (ADP-ribose) polymerase 1 (PARP-1) activity stimulated by endotoxin, which in turn induced apoptosis-inducing factor (AIF)-independent but PARP-1 dependent programmed cell death. Elevated PARP-1 activity triggered a cascade of molecular events, including PAR polymer release from the nucleus and the nicotinamide adenine dinucleotide (NAD+) and ATP depletion. Interestingly, translocation of AIF, a biochemical signature for PARP-1-dependent parthanatos, was not observed in the present study, suggesting a non-canonical mechanism of CD4 T cells parthanatos. In this study, we also identify a STING-mediated mechanism of necrotic cell death in CD4 T cells in septic animals. Furthermore, we revealed wider effects of STING on the mortality in mice when PARP-1 gene inhibited. These findings reveal that STING signaling and targeting PARP-1/PAR pathway in CD4 T cells may present a new therapeutic strategy for the treatment of acute systemic inflammatory diseases.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Poli(ADP-Ribose) Polimerase-1
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Inflamação
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Proteínas de Membrana
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Necrose
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Int Immunopharmacol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China