NLPR3 inflammasome activation results in loss of suppressive function in the MDSCs. Blockade of ATP signaling via intraperitoneal injection of apyrase or administration of P2x7 inhibitor A-438079 can abrogate NLRP3 inflammasome activation and restore MDSC suppressive function. IL-1β release can be visualized in vivo through the use of an IDOL transgenic mouse strain (IDOL.tg), in which IL-1β activation results in luciferase production that can be detected with bioluminescent imaging. When MDSCs were co-infused with Tregs, overall survival was improved and inflammasome activation was abrogated as assessed by bioluminescent imaging. The effects of IL-1β and IL-18 released from MDSCs have been associated with T-cell suppression and T-cell activation: blockade of IL-1β resulted in amelioration of GVHD,⁸  IL-1β KO donor MDSCs were inferior to wild-type MDSCs in suppressing GVHD (study by Koehn et al), addition of IL-1β enhanced MDSC suppressive function (study by Koehn et al), and administration of IL-18 can improve survival and decrease GVHD severity.⁷  Transfer of myeloid differentiation primary response 88 (MyD88) KO or transfer of double-KO MyD88/TIFF MDSCs did not result in improved survival over infusion of wild-type MDSCs. NLR family CARD domain-containing 4 (NLRC4) KO and administration of absent in melanoma 2 (AIM2) KO MDSCs resulted in improved aGVHD but offered no additional protection compared with wild-type MDSCs, whereas infusion of NRLP3 KO MDSCs resulted in a significant survival advantage. ASC, adaptor protein apoptosis-associated speck-like protein–containing caspase activation and recruitment domain (CARD); DAMPS, damage-associated molecular patterns; NFκB, nuclear factor κ light-chain enhancer of activated B cells; P2x7R, B6.129P2-P2rx7tm1Gab/J [mouse cell line]; PAMPS, pathogen-associated molecular patterns; ROS, reactive oxygen species; TLRs, Toll-like receptors; TRIF, TIR-domain-containing adapter-inducing interferon-β.