Journal
CANCER IMMUNOLOGY RESEARCH
Volume 8, Issue 8, Pages 1085-1098Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-19-0653
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Funding
- National Health and Medical Research Council (NHMRC)
- NHMRC [1078671, 1173958]
- National Health and Medical Research Council of Australia [1173958, 1078671] Funding Source: NHMRC
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The adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD) is known to facilitate caspase-1 activation, which is essential for innate host immunity via the formation of the inflammasome complex, a multiprotein structure responsible for processing IL1 beta b and IL18 into their active moieties. Here, we demonstrated that ASC-deficient CD8(+) T cells failed to induce severe graft-versus-host disease (GVHD) and had impaired capacity for graft rejection and graft-versus-leukemia (GVL) activity. These effects were inflammasome independent because GVHD lethality was not altered in recipients of caspase-1/11-deficient T cells. We also demonstrated that ASC deficiency resulted in a decrease in cytolytic function, with a reduction in granzyme B secretion and CD107a expression by CD8(+) T cells. Altogether, our findings highlight that ASC represents an attractive therapeutic target for improving outcomes of clinical transplantation.
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