期刊
EMBO JOURNAL
卷 39, 期 19, 页码 -出版社
WILEY
DOI: 10.15252/embj.2020105071
关键词
CARD8; inflammasome; pyroptosis; T cell; Val-boroPro
资金
- Else Kroner-Forschungskolleg: Cancer Immunotherapy
- FoFoLe program of the LMU
- ERC [ERC-2014-CoG -647858 GENESIS]
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [TRR 237/A09, SFB 1335/P015, SPP 1923]
- Projekt DEAL
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 blockingDPPs using Val-boroPro triggers a lytic form of cell death in primary humanCD4 andCD8 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 theCARD8-caspase-1-GSDMDaxis. Moreover,DPP9 constitutes the relevantDPPrestrainingCARD8 activation. Interestingly, thisCARD8-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.
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