Journal article
ASC modulates CTL cytotoxicity and transplant outcome independent of the inflammasome
M Cheong, KH Gartlan, JS Lee, SK Tey, P Zhang, RD Kuns, CE Andoniou, JP Martins, K Chang, VR Sutton, G Kelly, A Varelias, S Vuckovic, KA Markey, GM Boyle, MJ Smyth, CR Engwerda, KPA MacDonald, JA Trapani, MA Degli-Esposti Show all
Cancer Immunology Research | AMER ASSOC CANCER RESEARCH | Published : 2020
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 IL1β 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-versusleukemia (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 d..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
This study was supported by research grants from the National Health and Medical Research Council (NHMRC). M. Cheong was a Leukaemia Foundation PhD Fellow. M.J. Smyth was supported by an NHMRC Senior Principal Research Fellowship (1078671) and Investigator Grant (1173958). K.P.A. MacDonald is a Cancer Council of Queensland Fellow. C.R. Engwerda and M.A. Degli-Esposti are NHMRC Principal Research Fellows. J.A. Trapani is a Rosie Lew Fellow of the Peter MacCallum Cancer Foundation. M. Koyama was a Leukaemia Foundation Postdoctoral Fellow. G.R. Hill was an NHMRC Australian Fellow and QLD Health Senior Clinical Research Fellow. The authors thank Paula Hall, Michael Rist, and Grace Chojnowski for cell sorting.