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Supplementary Figure S1 from ASC Modulates CTL Cytotoxicity and Transplant Outcome Independent of the Inflammasome

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posted on 2023-04-04, 01:00 authored by Melody Cheong, Kate H. Gartlan, Jason S. Lee, Siok-Keen Tey, Ping Zhang, Rachel D. Kuns, Christopher E. Andoniou, Jose Paulo Martins, Karshing Chang, Vivien R. Sutton, Greg Kelly, Antiopi Varelias, Slavica Vuckovic, Kate A. Markey, Glen M. Boyle, Mark J. Smyth, Christian R. Engwerda, Kelli P.A. MacDonald, Joseph A. Trapani, Mariapia A. Degli-Esposti, Motoko Koyama, Geoffrey R. Hill

Supplementary Figure S1: GVHD survival of lethally-irradiated (day 0, 1000cGy split dose) B6.WT, B6.ASC-/- or B6.NLRP3-/- recipients transplanted with BALB/c BM (5x106) and T cells (5x106). The non-GVHD control group received TCD BM cells (5x106) only. Results combined from 2 independent experiments (n = 20 per T cell-replete group, n = 8 for TCD BM group). ****P < 0.0001; B6.NLRP3-/- vs. B6.WT. Results are presented as means {plus minus} SEM.

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ARTICLE 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-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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