CARD8 inflammasome activation triggers pyroptosis in human T cells
| Autor: | Veit Hornung, Yiming Cheng, Andreas Linder, Stefan Bauernfried, Christophe Jung, Oliver T. Keppler, Manuel Albanese |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
CD4-Positive T-Lymphocytes
Programmed cell death CARD8 Inflammasomes T cell Immunology Biology CD8-Positive T-Lymphocytes Lymphocyte Activation General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 0302 clinical medicine inflammasome medicine Cytotoxic T cell Humans Dipeptidyl-Peptidases and Tripeptidyl-Peptidases Molecular Biology 030304 developmental biology 0303 health sciences General Immunology and Microbiology General Neuroscience pyroptosis Pyroptosis Intracellular Signaling Peptides and Proteins Myeloid leukemia Inflammasome Articles Phosphate-Binding Proteins Acquired immune system Cell biology Neoplasm Proteins CARD Signaling Adaptor Proteins medicine.anatomical_structure Lytic cycle Val‐boroPro 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | The EMBO Journal |
| ISSN: | 1460-2075 0261-4189 |
| Popis: | 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. Inflammatory cell death, best studied in myeloid immune cells, can also be triggered in T cells depending specifically on the CARD8 inflammosome/caspase‐1/gasdermin‐D axis. |
| Databáze: | OpenAIRE |
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