Abstract

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 IL1ß 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.

Authors	Cheong, Melody; Gartlan, Kate H; Lee, Jason S; Tey, Siok-Keen; Zhang, Ping; Kuns, Rachel D; Andoniou, Christopher E; Martins, Jose Paulo; Chang, Karshing; Sutton, Vivien R; Kelly, Greg; Varelias, Antiopi; Vuckovic, Slavica; Markey, Kate A; Boyle, Glen M; Smyth, Mark J; Engwerda, Christian R; MacDonald, Kelli P A; Trapani, Joseph A; Degli-Esposti, Mariapia A; Koyama, Motoko; Hill, Geoffrey R
Journal	Cancer Immunology Research
Pages	1085-1098
Volume	8
Date	1/05/2020
Grant ID
Funding Body	National Health and Medical Research Council (NHMRC)
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1158/2326-6066.CIR-19-0653
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