AIM2 (Absent In Melanoma 2)

Moreover, DNA-LNPs synergized with anti-PD-L1, substantially extending animal survival in both ICI-responsive and ICI-resistant tumor models. These findings position DNA-LNPs as a promising immunotherapy strategy, either alone or in combination with ICI therapies, to enhance antitumor immunity across diverse cancer types.

Our results demonstrate that GBP2 expression is significantly upregulated in LN and promotes podocyte pyroptosis, likely contributing to renal injury. These findings suggest that GBP2 facilitates the progression of pediatric LN by activating the pyroptotic pathway and triggering the release of inflammatory cytokines.

Moreover, we found that expressing mitochondrial association factor 1 (MAF1I) from the hyper-virulent type I strain in type II T. gondii significantly inhibited the release of mtDNA into the host cell cytosol and reduced inflammasome activation. These data indicate that T. gondii infection in the context of IFN-γ signaling leads to AIM2 inflammasome activation by host mtDNA, a process that is competitively inhibited by MAF1I-mediated mitochondrial recruitment to the parasitophorous vacuole.

These events are coordinated by reduced interferon gamma signaling, which enhances collagen deposition while decreasing expression of efferocytotic genes. Our findings challenge the prevailing notion that IL-18 inhibition stabilizes atherosclerotic plaques and provide new mechanistic insight into the interplay among inflammasome biology, adaptive immunity, and plaque stability.

These results provide new insights into the cardiovascular and molecular basis of sex differences in hypertension, suggesting distinct neurohumoral autonomic profile in males, whereas in females a greater anti-inflammatory component. These findings offer a valuable framework for developing future sex-specific therapeutic strategies.

Aggressive LDL lowering reverses inflammasome activation and induces pro-resolving changes in macrophages in Jak2VF MPN, halting atherosclerosis progression and promoting features of plaque stabilization. These findings suggest that aggressive LDL cholesterol lowering could reverse atherosclerotic cardiovascular disease (ACVD) risk in individuals with JAK2VF CHIP or MPN.

Using both clinical samples and experimental models, we demonstrate that the cell-permeable derivative dimethyl-α-ketoglutarate (DM-α-KG) exacerbates lipopolysaccharide (LPS)-induced tissue injury and cell death, whereas isocitrate dehydrogenase (IDH1) inhibition (IDH-305) or genetic ablation reduces α-KG levels and confers protection...These findings establish α-KG as a critical immunometabolic checkpoint in sepsis that licenses inflammatory cell death via TET2-mediated epigenetic control of AIM2. Our work not only elucidates a novel α-KG/TET2/AIM2 signaling axis in sepsis pathogenesis but also highlights the therapeutic potential of targeting this pathway to modulate immune responses.

This study demonstrates that GLA exerts neuroprotective effects by activating the Nrf2/HO-1 antioxidant pathway and inhibiting AIM2 inflammasome-mediated pyroptosis. These findings suggest that GLA is a candidate drug with multi-target therapeutic potential, likely possessing clinical value for the treatment of SCI.

A novel pathway by which serum type-I IFN propagates innate immune dysfunction in SLE via the STAT1-STAT2/AIM2 inflammasome axis in monocytes has been revealed.

In summary, multimodal MRI enables dynamic monitoring of IP after CIRI in vivo and effectively evaluates the neuroprotective effects of Mel on IP. Mel broadens the time window for CIRI rescue and exerts a neuroprotective effect by downregulating AIM2 expression in neurons, thereby suppressing PANoptotic neuronal death in the IP areas and alleviating brain injury in rats with CIRI.

Such tools provide an important first step in identifying novel mediators of disease pathogenesis and likely hold the key for the discovery of potential treatment targets for BKPyVAN in the future.

This mechanism further exacerbates interstitial fibrosis by promoting the paracrine secretion of interleukin-6 and transforming growth factor-beta, which induces epithelial-mesenchymal transition (EMT) in adjacent tubular cells. These findings represent the first demonstration of the TNF-α/STAT1/AIM2 axis in triggering PANoptosis and its downstream EMT-fibrosis cascade, offering novel therapeutic targets for CAD intervention.