The complex role of AIM2 in autoimmune diseases and cancers

Zhu, Huan; Zhao, Ming; Chang, Christopher; Chan, Vera Sau-Fong; Lu, Qianjin; Wu, Haijing

doi:10.1002/iid3.443

Cited by 31 publications

(15 citation statements)

References 162 publications

(423 reference statements)

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“…Following fracture, the expression of Il1b and Il18 mRNA was induced in WT but not Gsdmd -/- mice ( Figure 4C–D ), suggesting a feedback mechanism whereby these cytokines secreted though GSDMD pores amplified their own expression. Since NLRP3 and absent in melanoma 2 (AIM2) inflammasomes, which sense plasma stimuli such as membrane perturbations and DNA, respectively, are implicated in the maturation of IL-1β, IL-18, and GSDMD ( Xiao et al, 2018 ; Xiao et al, 2020 ; Zhu et al, 2021 ), we also analyzed the expression of these sensors. Levels of Nlrp3 and Aim2 to some extent ( Figure 4C–D ) as well as those of Asc and caspase-1 ( Figure 4—figure supplement 1A, B ) were comparable between WT and Gsdmd -/- samples in homeostatic conditions.…”

Section: Resultsmentioning

confidence: 99%

Fracture healing is delayed in the absence of gasdermin-interleukin-1 signaling

Sun

Chün²,

Xiao³

et al. 2022

eLife

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IL-18. Excessive GSDM-mediated pore formation can compromise the integrity of the plasma membrane thereby causing the lytic inflammatory cell death, pyroptosis. We found that GSDMD and GSDME were the only GSDMs that were readily expressed in bone microenvironment. Therefore, we tested the hypothesis that GSDMD and GSDME are implicated in fracture healing owing to their role in the obligatory inflammatory response following injury. We found that bone callus volume and biomechanical properties of injured bones were significantly reduced in mice lacking either GSDM compared with wild-type (WT) mice, indicating that fracture healing was compromised in mutant mice. However, compound loss of GSDMD and GSDME did not exacerbate the outcomes, suggesting shared actions of both GSDMs in fracture healing. Mechanistically, bone injury induced IL-1β and IL-18 secretion in vivo, a response that was mimicked in vitro by bone debris and ATP, which function as inflammatory danger signals. Importantly, the secretion of these cytokines was attenuated in conditions of GSDMD deficiency. Finally, deletion of IL-1 receptor reproduced the phenotype of Gsdmd or Gsdme deficient mice, implying that inflammatory responses induced by the GSDM-IL-1 axis promote bone healing after fracture.

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Section: Resultsmentioning

confidence: 99%

Fracture healing is delayed in the absence of gasdermin-interleukin-1 signaling

Sun

Chün²,

Xiao³

et al. 2022

eLife

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“…4c,d), suggesting a feedback mechanism whereby these cytokines secreted though GSDMD pores amplified their own expression. Since NLRP3 and absent in melanoma 2 (AIM2) inflammasomes, which sense plasma stimuli such as membrane perturbations and DNA, respectively, are implicated in the maturation of IL-1β, IL-18, and GSDMD (26, 29, 45), we also analyzed the expression of these sensors. Levels of Nlrp3 and Aim2 to some extent (Fig.…”

Section: Resultsmentioning

confidence: 99%

Fracture healing is delayed in the absence of gasdermin signaling

Mbalaviele

Sun

Wang

et al. 2021

Preprint

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Amino-terminal fragments from proteolytically cleaved gasdermins (GSDMs) form plasma membrane pores that enable the secretion of interleukin-1β (IL-1β) and IL-18. Excessive GSDM- mediated pore formation can compromise the integrity of the plasma membrane thereby causing the lytic inflammatory cell death, pyroptosis. We found that GSDMD and GSDME were the only GSDMs that were readily expressed in bone microenvironment. Therefore, we tested the hypothesis that GSDMD and GSDME are implicated in fracture healing owing to their role in the obligatory inflammatory response following injury. We found that bone callus volume and biomechanical properties of injured bones were significantly reduced in mice lacking either GSDM compared with wild-type (WT) mice, indicating that fracture healing was compromised in mutant mice. However, compound loss of GSDMD and GSDME did not exacerbate the outcomes, suggesting shared actions of both GSDMs in fracture healing. Mechanistically, bone injury induced IL-1β and IL-18 secretion in vivo, a response that was mimicked in vitro by bone debris and ATP, which function as inflammatory danger signals. Importantly, the secretion of these cytokines was attenuated in conditions of GSDMD deficiency. Finally, deletion of IL-1 receptor reproduced the phenotype of Gsdmd or Gsdme deficient mice, implying that inflammatory responses induced by the GSDM-IL-1 axis promote bone healing after fracture.

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“…It can regulate the production of IL-1β and IL-18 to influence T reg cell accumulation and tumor growth. In addition, T cell reactivity against AIM2 has also been found in melanoma, indicating that AIM2-derived peptides can serve as relevant targets for immunomonitoring ( Zhu et al, 2021 ). In renal cancer, AIM2 can induce the transformation of anti-inflammatory M2 to pro-inflammatory M1 by enhancing the inflammasome pathway, thus inhibiting tumor progression ( Chai et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Generation and Analysis of Pyroptosis-Based and Immune-Based Signatures for Kidney Renal Clear Cell Carcinoma Patients, and Cell Experiment

et al. 2022

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Background: Pyroptosis is a programmed cell death caused by inflammasomes, which is closely related to immune responses and tumor progression. The present study aimed to construct dual prognostic indices based on pyroptosis-associated and immune-associated genes and to investigate the impact of the biological signatures of these genes on Kidney Renal Clear Cell Carcinoma (KIRC).Materials and Methods: All the KIRC samples from the Cancer Genome Atlas (TCGA) were randomly and equally divided into the training and testing datasets. Cox and Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis were used to screen crucial pyroptosis-associated genes (PAGs), and a pyroptosis-associated genes prognostic index (PAGsPI) was constructed. Immune-associated genes (IAGs) related to PAGs were identified, and then screened through Cox and LASSO regression analyses, and an immune-associated genes prognostic index (IAGsPI) was developed. These two prognostic indices were verified by using the testing and the Gene Expression Omnibus (GEO) datasets and an independent cohort. The patients’ response to immunotherapy was analyzed. A nomogram was constructed and calibrated. qRT-PCR was used to detect the expression of PAGs and IAGs in the tumor tissues and normal tissues. Functional experiment was carried out.Results: 86 PAGs and 1,774 differentially expressed genes (DEGs) were obtained. After intersecting PAGs with DEGs, 22 differentially expressed PAGs (DEPAGs) were included in Cox and LASSO regression analyses, identifying 5 crucial PAGs. The PAGsPI was generated. Patients in the high-PAGsPI group had a poor prognosis. 82 differentially expressed IAGs (DEIAGs) were highly correlated with DEPAGs. 7 key IAGs were screened out, and an IAGsPI was generated. Patients in the high-IAGsPI group had a poor prognosis. PAGsPI and IAGsPI were verified to be robust and reliable. The results revealed patients in low-PAGsPI group and high-IAGsPI group may be more sensitive to immunotherapy. The calibrated nomogram was proved to be reliable. An independent cohort study also proved that PAGsPI and IAGsPI performed well in prognosis prediction. We found that the expression of AIM2 may affect proliferation of KIRC cells.Conclusion: PAGsPI and IAGsPI could be regarded as potential biomarkers for predicting the prognosis of patients with KIRC.

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The complex role of AIM2 in autoimmune diseases and cancers

Cited by 31 publications

References 162 publications

Fracture healing is delayed in the absence of gasdermin-interleukin-1 signaling

Fracture healing is delayed in the absence of gasdermin-interleukin-1 signaling

Fracture healing is delayed in the absence of gasdermin signaling

Generation and Analysis of Pyroptosis-Based and Immune-Based Signatures for Kidney Renal Clear Cell Carcinoma Patients, and Cell Experiment

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