CARD8 inflammasome activation triggers pyroptosis in human T cells.
EMBO J
; 39(19): e105071, 2020 10 01.
Article
em En
| MEDLINE
| ID: mdl-32840892
ABSTRACT
Inflammasomes execute a unique type of cell death known as pyroptosis. Mostly characterized in myeloid cells, caspase-1 activation downstream of an inflammasome sensor results in the cleavage and activation of gasdermin D (GSDMD), which then forms a lytic pore in the plasma membrane. Recently, CARD8 was identified as a novel inflammasome sensor that triggers pyroptosis in myeloid leukemia cells upon inhibition of dipeptidyl-peptidases (DPP). Here, we show that blocking DPPs using Val-boroPro triggers a lytic form of cell death in primary human CD4 and CD8 T cells, while other prototypical inflammasome stimuli were not active. This cell death displays morphological and biochemical hallmarks of pyroptosis. By genetically dissecting candidate components in primary T cells, we identify this response to be dependent on the CARD8-caspase-1-GSDMD axis. Moreover, DPP9 constitutes the relevant DPP restraining CARD8 activation. Interestingly, this CARD8-induced pyroptosis pathway can only be engaged in resting, but not in activated T cells. Altogether, these results broaden the relevance of inflammasome signaling and associated pyroptotic cell death to T cells, central players of the adaptive immune system.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
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Linfócitos T CD4-Positivos
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Linfócitos T CD8-Positivos
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Proteínas Adaptadoras de Sinalização CARD
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Inflamassomos
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Proteínas de Neoplasias
Limite:
Humans
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2020
Tipo de documento:
Article