NLRP3 Deficiency in Macrophages Ameliorates Gut Inflammation and Augments Treg Population In Vivo and In Vitro

This is the authors' abstract. We don't add key points for this paper.

The NLRP3 inflammasome, prominently expressed in macrophages, has garnered significant attention as a contributing factor to graft-versus-host disease (GVHD). In this study, we established an allogeneic hematopoietic cells transplantation mice model using NLRP3 knockout (NLRP3-/-) and wild-type C57BL/6 mice as recipients to investigate the impact underlying mechanisms of NLRP3 deficiency on gut GVHD. Results clearly revealed that NLRP3-/- recipients exhibited reduced gut inflammation infiltration, accompanied by an increased number of Tregs and accelerated white blood cell recovery. Moreover, the loss of NLRP3 function led to decreased protein levels of macrophage-related molecules in the gut, such as interleukin 1β (IL-1β), caspase-1, CD68 and CD11b, alongside an augmented presence of M2 macrophages in the bone marrow. In vitro experiments using bone marrow-derived macrophages (BMDMs) confirmed that NLRP3 deficiency led to lower levels of inflammasome-dependent cytokines IL-1β, pan-inflammatory factors IL-6, and chemotactic factors CCL3/CCL4. Furthermore, NLRP3-/- in BMDMs demonstrated an ability to effectively induce apoptosis and increase the proportion of Tregs in the mixed lymphocyte reaction system. Overall, our study elucidates the significance of macrophages in regulating gut inflammation through the NLRP3 inflammasome pathway, highlighting the potential therapeutic benefits of targeting NLRP3 or macrophages in the treatment of GVHD.