Affinage

AIM2

Interferon-inducible protein AIM2 · UniProt O14862

Length
343 aa
Mass
39.0 kDa
Annotated
2026-06-09
100 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AIM2 is a cytosolic double-stranded DNA sensor that nucleates a caspase-1-activating inflammasome, coupling detection of aberrant DNA to inflammatory cell death (PMID:19158675, PMID:19158676). It binds dsDNA through its HIN200/OB domain and engages ASC through its N-terminal pyrin domain, oligomerizing upon DNA stimulation to drive ASC pyroptosome formation, caspase-1 activation, and pyroptotic death (PMID:19158675, PMID:19158676). Nucleic-acid specificity arises from filament assembly: AIM2 binds diverse nucleic acids but preferentially forms ordered filaments on dsDNA in a duplex-length-dependent manner, and only dsDNA-templated filaments — built through primary and secondary nucleation rather than diffusive scanning — trigger downstream ASC polymerization (PMID:36864667, PMID:38042863). Beyond IL-1β/IL-18 maturation, AIM2 sensing of nuclear radiation-induced DNA damage and of cytosolic mitochondrial or replication-stress DNA links genotoxic and metabolic stress to inflammasome-driven tissue pathology, and a gasdermin-D-dependent pyroptotic arm clears DNA-damaged cells during neurodevelopment without cytokine output (PMID:27846608, PMID:29033131, PMID:33731931, PMID:32350463). The inflammasome also expands into larger death-signaling assemblies, recruiting caspase-8 and forming a multiprotein PANoptosome with pyrin, ZBP1, RIPK1/3, FADD and caspase-1/8 to drive PANoptosis during infection (PMID:23645208, PMID:34471287). AIM2 abundance and complex assembly are gated by ubiquitination: TRIM11 ubiquitinates AIM2 and recruits p62 for selective autophagic degradation, USP21 deubiquitinates AIM2 upon DNA stimulation to stabilize it and permit AIM2–ASC assembly, and K63-ubiquitination of ASC marks the AIM2–ASC complex for p62-mediated autophagy (PMID:27498865, PMID:34470856, PMID:37647255). AIM2 additionally performs inflammasome-independent functions across cell types — restraining type I IFN signaling by sequestering IFI205 from STING and by inhibiting cGAS/DNA-PK–AKT–IRF3 axes in microglia (PMID:28679751, PMID:33710283, PMID:35959803), binding the RACK1–PP2A complex to suppress AKT–mTOR signaling and stabilize Treg cells (PMID:33505023), binding the microtubule end-binding protein EB1 to promote epithelial migration and tumorigenesis (PMID:34489308), and modulating mitochondrial dynamics via MFN2 (PMID:32005973).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2009 High

    Established the core identity of AIM2 as the missing cytosolic DNA receptor that converts dsDNA detection into caspase-1 activation, defining a domain logic (DNA-binding HIN200/OB plus ASC-engaging pyrin) for the inflammasome.

    Evidence siRNA knockdown and domain-mapping in mouse/human cells plus reconstitution in non-responsive HEK293T, with caspase-1 and ASC pyroptosome readouts

    PMID:19158675 PMID:19158676

    Open questions at the time
    • Atomic basis of DNA-binding specificity not yet resolved
    • How oligomerization nucleates ASC was not mechanistically defined
  2. 2013 High

    Showed the AIM2 inflammasome is not solely pyroptotic — it recruits caspase-8 as an apical caspase to also drive apoptosis, broadening its death-signaling repertoire.

    Evidence knockdown, live-cell imaging, Co-IP, and immunofluorescence of caspase-8 at ASC specks

    PMID:23645208

    Open questions at the time
    • Determinants choosing apoptotic vs pyroptotic outcome unclear
    • Direct caspase-8 binding to ASC PYD not structurally defined
  3. 2016 High

    Defined post-translational and metabolic control of AIM2: TRIM11/p62 autophagic degradation limits activation, while PKM2-driven glycolysis and EIF2AK2 phosphorylation promote it, and STING-pathway competition links AIM2 to IFN restriction.

    Evidence Co-IP, K458 mutagenesis, autophagy/p62 assays, conditional PKM2 KO, EIF2AK2 inhibition, and macrophage STING/IFN assays

    PMID:27409673 PMID:27498865 PMID:27779186

    Open questions at the time
    • Ubiquitin linkage type on AIM2 not specified
    • How glycolytic flux mechanistically gates inflammasome assembly unresolved
  4. 2016 High

    Demonstrated AIM2 senses DNA damage in the nucleus and cholesterol-driven mtDNA release in cytosol, expanding its triggers from foreign DNA to endogenous genotoxic and metabolic stress with defined in vivo pathology.

    Evidence AIM2-KO and Ch25h-KO mice, irradiation and cholesterol-loading models, mtDNA cytosolic release and IL-1β assays

    PMID:27846608 PMID:29033131

    Open questions at the time
    • How nuclear AIM2 accesses damaged DNA mechanistically unclear
    • Whether the same filament mechanism operates on endogenous DNA not tested
  5. 2017 Medium

    Revealed an inflammasome-independent role in restraining type I IFN by sequestering the ALR IFI205 away from STING, positioning AIM2 as a negative regulator of cytosolic DNA-triggered IFN.

    Evidence ALR overexpression/knockdown, IFN induction assays, and AIM2-IFI205 Co-IP

    PMID:28679751

    Open questions at the time
    • Single-lab Co-IP without reciprocal structural validation
    • Human relevance of mouse IFI205 axis untested
  6. 2020 Medium

    Extended AIM2's inflammasome-independent functions into adaptive and neural contexts — restraining AKT-mTOR via RACK1-PP2A in Treg cells, suppressing DNA-PK-AKT3 and cGAS-AKT-IRF3 signaling in microglia, and modulating MFN2-dependent mitochondrial dynamics in tumor cells.

    Evidence T-cell- and microglia-conditional/KO mice, Co-IP of AIM2-RACK1-PP2A, AKT3/IRF3 phospho-assays, MFN2/ROS and MAPK readouts in NSCLC with xenografts

    PMID:32005973 PMID:33505023 PMID:33710283 PMID:35959803

    Open questions at the time
    • Direct vs indirect engagement of these kinase axes not always resolved
    • How a DNA sensor relocalizes to mitochondria or cytosolic scaffolds unclear
  7. 2020 High

    Showed the AIM2 inflammasome contributes to CNS homeostasis via a gasdermin-D-dependent pyroptotic arm that clears DNA-damaged neurons during development, dissociating cell-death function from IL-1/IL-18 cytokine output.

    Evidence AIM2-KO and GSDMD-KO mice, DNA-damage agents, cell-death quantification, and behavioral analysis

    PMID:32350463

    Open questions at the time
    • Trigger for developmental AIM2 activation not defined
    • Why cytokine output is bypassed mechanistically unclear
  8. 2021 High

    Defined ubiquitin-switch and complex-assembly control: USP21 deubiquitinates AIM2 upon DNA sensing to stabilize it and enable AIM2-ASC assembly without affecting DNA binding; AIM2 also nucleates a multiprotein PANoptosome integrating pyrin and ZBP1 sensing during infection.

    Evidence Co-IP, ubiquitination/proteasome assays, AIM2-ASC and DNA-binding assays, and reciprocal Co-IP plus KO mice in HSV-1/F. novicida infection

    PMID:34470856 PMID:34471287

    Open questions at the time
    • E3 ligase opposing USP21 in this context not identified
    • Stoichiometry and order of PANoptosome assembly not resolved
  9. 2021 High

    Linked endogenous DNA-damage/replication-stress sensing by AIM2 to disease pathology, including JAK2V617F clonal-hematopoiesis-driven atherosclerosis, and uncovered transcriptional and nuclear-chromatin roles.

    Evidence Jak2VF macrophage expression with AIM2/caspase-1-11/GSDMD KO mice and scRNA-seq; STAT3 ChIP on AIM2 promoter and AIM2-EB1 Co-IP; ALR-KO chromatin-binding and DNA-repair assays

    PMID:33731931 PMID:34489308 PMID:34658166

    Open questions at the time
    • How nuclear AIM2 interferes with chromatin decompaction mechanistically unclear
    • Direct vs scaffold role of AIM2-EB1 in migration not structurally resolved
  10. 2023 High

    Resolved the biophysical basis of AIM2 specificity and the ubiquitin code controlling its turnover — dsDNA-length-dependent filament assembly via primary and secondary nucleation gates ASC polymerization, and K63-ubiquitination of ASC (controlled by USP50) routes the AIM2-ASC complex to p62 autophagy.

    Evidence in vitro reconstitution, cryo-EM, single-molecule optical-trap kinetics, DARTS, and site-directed mutagenesis of ASC K158/161 and USP50 Cys53

    PMID:36864667 PMID:37647255 PMID:38042863

    Open questions at the time
    • How filament geometry templates ASC nucleation structurally undefined
    • In vivo relevance of single-molecule kinetics not established
  11. 2023 Medium

    Mapped further inflammasome-independent disease roles — TRIM11-driven autophagic degradation of AIM2 tunes Treg differentiation in EAE, EIF2AK2-driven AIM2 upregulation activates PANoptosis in septic AKI, and AIM2 suppresses ferroptosis via FOXO3a-ACSL4.

    Evidence Co-IP, ubiquitination assays, AIM2-/TRIM11-/- mice in EAE, CLP model with knockdowns, and FOXO3a/ACSL4/ferroptosis assays

    PMID:36923928 PMID:37804507 PMID:39311631

    Open questions at the time
    • Whether EIF2AK2 directly stabilizes vs transcriptionally induces AIM2 not separated
    • Generality of ferroptosis suppression beyond RCC untested
  12. 2024 Medium

    Reinforced a mitochondrial, autophagy-modulating, inflammasome-independent function in which AIM2 dampens JNK/ERK signaling and oxidative stress to protect against drug-induced liver injury.

    Evidence AIM2-KO mice, hepatocyte overexpression, mitochondrial localization, autophagy and JNK/ERK phospho-assays, rapamycin treatment

    PMID:38429284

    Open questions at the time
    • Molecular partner at mitochondria not identified
    • Single-lab finding without reciprocal validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How AIM2 physically toggles between its canonical DNA-sensing inflammasome state and its diverse cytosolic, nuclear, and mitochondrial inflammasome-independent activities — and what determines this partitioning in a given cell — remains unresolved.
  • No unified structural model linking DNA-bound filaments to non-inflammasome scaffolding
  • Subcellular targeting signals directing AIM2 to nucleus vs mitochondria unknown
  • Direct vs indirect engagement of AKT/mTOR/IRF3 axes not consistently demonstrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 4 GO:0098772 molecular function regulator activity 4 GO:0140299 molecular sensor activity 3 GO:0060089 molecular transducer activity 2 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 2 GO:0005739 mitochondrion 2 GO:0005829 cytosol 2 GO:0005694 chromosome 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-9612973 Autophagy 4 R-HSA-73894 DNA Repair 2
Partners
ASC/PYCARDCASP8EB1IFI205MFN2RACK1TRIM11USP21
Complex memberships
AIM2 inflammasome (AIM2-ASC-caspase-1)AIM2-RACK1-PP2A complexPANoptosome (AIM2-pyrin-ZBP1-ASC-caspase-1/8-RIPK1/3-FADD)

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 AIM2 HIN200 domain binds cytosolic dsDNA, while the AIM2 pyrin domain associates with ASC to activate both NF-κB and caspase-1; knockdown of AIM2 abrogates caspase-1 activation in response to cytoplasmic dsDNA and vaccinia virus, identifying AIM2 as a cytosolic DNA receptor that forms a caspase-1-activating inflammasome with ASC. siRNA knockdown, domain-mapping experiments (HIN200 DNA binding, pyrin-ASC association), NF-κB and caspase-1 activation assays in mouse and human cells Nature High 19158675
2009 AIM2 senses cytoplasmic DNA via its OB (oligonucleotide/oligosaccharide-binding) domain, interacts with ASC through its pyrin domain to activate caspase-1, induces ASC pyroptosome formation and pyroptotic cell death; AIM2 oligomerizes upon DNA stimulation; stable expression in HEK293T cells confers DNA responsiveness. siRNA knockdown in human and mouse macrophages, stable AIM2 expression in HEK293T cells, ASC pyroptosome formation assay, caspase-1 activation assay Nature High 19158676
2013 AIM2 inflammasome activates both caspase-8 and caspase-1, leading to apoptotic and pyroptotic cell death; caspase-8 is the apical caspase in AIM2-dependent apoptosis (with little requirement for caspase-9); procaspase-8 localizes to ASC inflammasome specks and binds directly to the pyrin domain of ASC. Gene knockdown, live-cell imaging, co-immunoprecipitation, immunofluorescence localization of caspase-8 to ASC specks Cell death and differentiation High 23645208
2016 TRIM11 binds AIM2 via its PS domain, undergoes auto-polyubiquitination at K458, and recruits the autophagic cargo receptor p62, thereby delivering AIM2 to autophagosomes for selective autophagic degradation; this suppresses AIM2 inflammasome activation. Co-immunoprecipitation, mutagenesis (K458 ubiquitination site), autophagy assays, p62 pulldown, gene knockdown Cell reports High 27498865
2016 AIM2 senses radiation-induced DNA damage in the nucleus to mediate caspase-1-dependent inflammasome activation and cell death; AIM2-deficient mice are protected from irradiation-induced gastrointestinal syndrome and hematopoietic failure. AIM2-knockout mice, irradiation model, nuclear localization studies, caspase-1 activation assays Science High 27846608
2016 PKM2-mediated aerobic glycolysis promotes AIM2 inflammasome activation by modulating EIF2AK2 phosphorylation in macrophages; pharmacological and genetic inhibition of PKM2 or EIF2AK2 attenuates AIM2 inflammasome activation. PKM2 knockout (myeloid-conditional), EIF2AK2 pharmacological and genetic inhibition, inflammasome activation assays (IL-1β, IL-18 secretion), phosphorylation analysis Nature communications High 27779186
2017 Cholesterol-25-hydroxylase (Ch25h) produces 25-hydroxycholesterol (25-HC) to repress SREBP2 and cholesterol synthesis; increased macrophage cholesterol content triggers AIM2-dependent IL-1β release independently of crystals; Ch25h deficiency leads to mitochondrial DNA release into the cytosol which activates AIM2; AIM2 deficiency rescues the increased inflammasome activity in Ch25h-/- macrophages. Ch25h-/- and AIM2-/- genetic mouse models, cholesterol loading experiments, mitochondrial DNA cytosolic release assay, IL-1β secretion assays Cell High 29033131
2017 AIM2 antagonizes mouse ALR IFI205-mediated interferon induction activity by sequestering IFI205 from STING, thus negatively regulating the cytosolic DNA-triggered type I IFN response. ALR overexpression and knockdown experiments, IFN induction assays, co-immunoprecipitation showing AIM2-IFI205 interaction mBio Medium 28679751
2019 AIM2 interacts with the RACK1-PP2A phosphatase complex in T regulatory cells to restrain AKT phosphorylation, attenuating mTOR and MYC signaling and glycolysis while promoting oxidative phosphorylation; this inflammasome-independent function promotes Treg cell stability. RNA-seq, biochemical co-immunoprecipitation (AIM2-RACK1-PP2A complex), metabolic assays (glycolysis/OXPHOS), AIM2-conditional KO in T cells, lineage tracing Nature High 33505023
2020 AIM2 negatively regulates the DNA-PK–AKT3 signaling axis in microglia in an inflammasome-independent manner, thereby controlling cGAS- and DNA-PK-synergistically induced neuroinflammation during experimental autoimmune encephalomyelitis. AIM2-/- mice, microglial-specific analysis, DNA-PK inhibitor treatment, AKT3 phosphorylation assays The Journal of experimental medicine Medium 33710283
2020 AIM2 inflammasome contributes to CNS homeostasis by regulating gasdermin-D-dependent pyroptosis (not IL-1/IL-18 cytokine production) to remove genetically compromised cells during neurodevelopment; AIM2 deficiency results in decreased neural cell death and excessive accumulation of DNA-damaged neurons in the adult brain. AIM2-knockout mice, gasdermin-D-knockout mice, DNA damage-inducing agents, cell death quantification, behavioral analysis Nature High 32350463
2020 AIM2 colocalized with mitochondria in NSCLC cells; AIM2 knockdown leads to MFN2 upregulation, enhanced mitochondrial fusion, decreased ROS production, and inactivation of MAPK/ERK signaling, reducing tumor cell proliferation independent of inflammasome activation. AIM2 knockdown/overexpression, mitochondrial colocalization (fluorescence), MFN2 protein analysis, ROS measurement, MAPK/ERK pathway assays, xenograft in vivo model Oncogene Medium 32005973
2021 AIM2 forms a large multi-protein PANoptosome complex with pyrin, ZBP1, ASC, caspase-1, caspase-8, RIPK3, RIPK1 and FADD to drive PANoptosis; AIM2 regulates pyrin and ZBP1 innate immune sensors during HSV-1 and Francisella novicida infection. Co-immunoprecipitation of multi-protein complex, AIM2/pyrin/ZBP1 knockout mice, cell death assays, infection models Nature High 34471287
2021 USP21 deubiquitinase binds to AIM2 upon DNA stimulation and deubiquitinates it, increasing AIM2 protein stability; in resting macrophages AIM2 is constitutively ubiquitinated and undergoes proteasomal degradation; USP21-mediated deubiquitination is required for AIM2-ASC complex assembly (but does not affect AIM2 DNA-binding ability). Co-immunoprecipitation, ubiquitination assays, proteasome inhibition, USP21 knockdown, AIM2-ASC complex formation assay, DNA-binding assay Journal of immunology High 34470856
2021 STAT3, activated by IL-11 cytokine signaling, transcriptionally upregulates AIM2 in gastric tumor epithelium; AIM2 physically interacts with microtubule end-binding protein EB1 to promote epithelial cell migration and tumourigenesis independent of inflammasome activity. ChIP (STAT3 binding to AIM2 promoter), Co-immunoprecipitation (AIM2-EB1 interaction), genetic AIM2 targeting in gp130F/F mouse model, xenograft, in vitro migration assays Gut High 34489308
2021 AIM2 deficiency in B cells leads to increased Blimp-1 expression and reduced Bcl-6 expression, regulating B-cell differentiation; AIM2 acts upstream of the Blimp-1–Bcl-6 axis (silencing Blimp-1 or Bcl-6 had no effect on AIM2 expression); IL-10 upregulates AIM2 expression via DNA demethylation. B cell-conditional AIM2 knockout mice, Western blot/qPCR for Blimp-1 and Bcl-6, siRNA knockdown of Blimp-1/Bcl-6, DNA methylation analysis Signal transduction and targeted therapy Medium 34521812
2021 AIM2 inflammasome activation in JAK2V617F macrophages is driven by oxidative DNA damage and DNA replication stress; Aim2 deficiency reduces atherosclerosis in clonal haematopoiesis models; deletion of caspase-1/11, gasdermin D, or AIM2 reverses adverse atherosclerotic changes. Jak2VF selective macrophage expression, Aim2-/- mice, caspase-1/11-/- and gasdermin D-/- mice, atherosclerosis quantification, DNA damage markers, scRNA-seq Nature High 33731931
2016 AIM2 inhibits STING-dependent selective autophagy and IFN-β secretion during M. bovis infection by competitively binding cytosolic mycobacterial DNA, thereby restricting STING-TBK1-dependent pathway activation. AIM2 knockdown/overexpression in macrophages, autophagy assays, STING pathway analysis, IFN-β secretion measurement Oncotarget Medium 27409673
2021 In microglia, AIM2 reduces cGAS-mediated antiviral inflammation by inhibiting AKT-IRF3 phosphorylation in an inflammasome-independent manner; microglial AIM2 deficiency exacerbates both MPTP-induced and transgenic PD models. AIM2-/- and bone marrow chimeric mice, MPTP model, RNA-sequencing, primary microglial transfection, AKT-IRF3 phosphorylation assays Glia Medium 35959803
2023 AIM2 filament assembly on dsDNA is essential for nucleic acid specificity: AIM2 binds various nucleic acids but preferentially assembles ordered filaments on dsDNA in a duplex length-dependent manner; only filaments assembled on dsDNA induce downstream ASC polymerization; oligomers on other nucleic acids fail to trigger ASC polymerization. In vitro biochemical filament assembly assays, cryo-EM structural analysis, ASC polymerization assays with different nucleic acid substrates Nucleic acids research High 36864667
2023 AIM2 assembly on dsDNA proceeds via two distinct mechanisms resembling primary nucleation (incoming AIM2 binds adjacent dsDNA) and secondary nucleation (incoming AIM2 directly contacts DNA-bound AIM2 assemblies); oligomer size can increase fourfold in seconds; single AIM2 molecules do not diffuse/scan along DNA. Single-molecule optical trap + confocal fluorescence microscopy, kinetic rate measurements of association and dissociation Nature communications High 38042863
2023 Pristimerin enhances K63-linked ubiquitin chains on PYCARD/ASC at K158/161 by binding the Cys53 site of deubiquitinase USP50, blocking USP50-mediated removal of these chains; the K63-ubiquitinated PYCARD/ASC serves as recognition signal for SQSTM1/p62-mediated autophagic degradation of the AIM2-PYCARD/ASC complex. Drug affinity responsive target stability (DARTS) assay, site-directed mutagenesis (Cys53, K158/161), Co-IP, ubiquitination assays, autophagy assays Autophagy High 37647255
2023 EIF2AK2 directly targets AIM2 protein (shown by Co-IP) and positively regulates AIM2 expression, thereby upregulating AIM2 to activate PANoptosis in septic AKI. Co-immunoprecipitation, siRNA knockdown of EIF2AK2 and AIM2, LDH cytotoxicity assay, CLP mouse model Renal failure Medium 39311631
2023 TRIM11 promotes selective autophagic degradation of AIM2 by inducing AIM2 ubiquitination and p62 binding in CD4+ T cells, attenuating Treg cell differentiation; AIM2 attenuates AKT and FOXO1 phosphorylation, MYC signaling, and glycolysis to promote Treg stability in this context. Co-immunoprecipitation (TRIM11-AIM2 interaction), ubiquitination assays, AIM2-/- and TRIM11-/- mice in EAE model, metabolic assays, T cell differentiation assays Cell reports High 37804507
2021 Nuclear AIM2-like receptors (ALRs) bind to chromatin and interfere with chromatin decompaction required for DNA repair, thereby inhibiting DNA repair and accelerating genome destabilization, micronuclei generation, and cell death; this function is uncoupled from their role in innate immunity/inflammasome. ALR-knockout mice, irradiation-induced bone marrow injury model, chromatin binding assays, DNA repair assays, micronuclei quantification Advanced science Medium 34658166
2014 HMGB1-DNA complex initially induces AIM2-dependent inflammasome activation and IL-1β release via RAGE; subsequently HMGB1-DNA complex triggers ATG5-dependent autophagy through RAGE, which functions as a negative feedback to limit AIM2 inflammasome activation. RAGE-blocking experiments, ATG5 knockdown, AIM2 inflammasome activation assays, IL-1β ELISA, autophagy assays Biochemical and biophysical research communications Medium 24971542
2022 AIM2 promotes FOXO3a phosphorylation and proteasome-mediated degradation, reducing FOXO3a transcriptional activation of ACSL4, thereby inhibiting ferroptosis to promote renal cell carcinoma progression in an inflammasome-independent manner. AIM2 knockdown/overexpression in RCC cells, FOXO3a phosphorylation and degradation assays, ACSL4 expression analysis, ferroptosis assays International journal of biological sciences Medium 36923928
2020 AIM2 inhibits colorectal cancer cell proliferation and migration through Gli1 suppression via a Smoothened-independent pathway, and regulates the AKT/mTOR/Gli1 signaling axis; AKT inhibition reverses increased Gli1 and EMT induced by AIM2 depletion. AIM2 knockdown/overexpression, Gli1 expression analysis, AKT inhibitor (Ly294002) treatment, proliferation/migration assays, Western blot Aging Medium 33291082
2022 AIM2 and IFI16 bind neutrophil extracellular traps (NETs) in vitro and in SLE renal tissues; ALR binding causes NETs to resist degradation by DNase I, suggesting extracellular ALR-NET interactions may promote sustained IFN signaling. Immunoprecipitation (autoantibody detection), immunofluorescence of ALR-NET binding, DNase I protection assay, confocal microscopy of SLE renal tissue eLife Medium 35608258
2024 AIM2 localizes to mitochondria in mouse hepatocytes; overexpression amplifies autophagy while dampening JNK phosphorylation; AIM2 deficiency in aged mice exacerbates APAP-induced liver injury by increasing oxidative stress and augmenting JNK/ERK phosphorylation, independent of inflammasome activation. AIM2-KO mice, AIM2 overexpression in hepatocytes, mitochondrial localization assay, autophagy assays, JNK/ERK phosphorylation analysis, rapamycin treatment Cell death discovery Medium 38429284

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 2131 19158675
2009 AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 1507 19158676
2021 AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host defence. Nature 635 34471287
2016 PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation. Nature communications 466 27779186
2013 AIM2 and NLRP3 inflammasomes activate both apoptotic and pyroptotic death pathways via ASC. Cell death and differentiation 439 23645208
2021 The AIM2 inflammasome exacerbates atherosclerosis in clonal haematopoiesis. Nature 398 33731931
2016 The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury. Science (New York, N.Y.) 325 27846608
2017 Oxysterol Restraint of Cholesterol Synthesis Prevents AIM2 Inflammasome Activation. Cell 294 29033131
2018 The AIM2 inflammasome: Sensor of pathogens and cellular perturbations. Immunological reviews 286 29247998
2015 AIM2 inflammasome in infection, cancer, and autoimmunity: Role in DNA sensing, inflammation, and innate immunity. European journal of immunology 286 26626159
2019 Role of AIM2 inflammasome in inflammatory diseases, cancer and infection. European journal of immunology 236 31372985
2020 AIM2 inflammasome surveillance of DNA damage shapes neurodevelopment. Nature 193 32350463
2020 AIM2 in health and disease: Inflammasome and beyond. Immunological reviews 192 32713036
2021 Perfluoroalkyl substance pollutants activate the innate immune system through the AIM2 inflammasome. Nature communications 182 34006824
2017 AIM2 inflammasome activation and regulation: A structural perspective. Journal of structural biology 180 28813641
2020 AIM2 inflammasome contributes to brain injury and chronic post-stroke cognitive impairment in mice. Brain, behavior, and immunity 164 32201254
2016 TRIM11 Suppresses AIM2 Inflammasome by Degrading AIM2 via p62-Dependent Selective Autophagy. Cell reports 149 27498865
2021 Structure, Activation and Regulation of NLRP3 and AIM2 Inflammasomes. International journal of molecular sciences 142 33467177
2021 AIM2 in regulatory T cells restrains autoimmune diseases. Nature 138 33505023
2023 Integrated NLRP3, AIM2, NLRC4, Pyrin inflammasome activation and assembly drive PANoptosis. Cellular & molecular immunology 137 38008850
2022 Tumor Treating Fields dually activate STING and AIM2 inflammasomes to induce adjuvant immunity in glioblastoma. The Journal of clinical investigation 121 35199647
2022 Overexpression of NAG-1/GDF15 prevents hepatic steatosis through inhibiting oxidative stress-mediated dsDNA release and AIM2 inflammasome activation. Redox biology 107 35504134
2017 AIM2 Inflammasome Is Critical for Influenza-Induced Lung Injury and Mortality. Journal of immunology (Baltimore, Md. : 1950) 100 28424239
2023 Immune regulator IRF1 contributes to ZBP1-, AIM2-, RIPK1-, and NLRP12-PANoptosome activation and inflammatory cell death (PANoptosis). The Journal of biological chemistry 91 37557956
2021 AIM2-driven inflammasome activation in heart failure. Cardiovascular research 86 34117866
2021 AIM2 controls microglial inflammation to prevent experimental autoimmune encephalomyelitis. The Journal of experimental medicine 84 33710283
2019 AIM2 gene silencing attenuates diabetic cardiomyopathy in type 2 diabetic rat model. Life sciences 83 30790610
2021 AIM2 deficiency in B cells ameliorates systemic lupus erythematosus by regulating Blimp-1-Bcl-6 axis-mediated B-cell differentiation. Signal transduction and targeted therapy 82 34521812
2021 The AIM2 and NLRP3 inflammasomes trigger IL-1-mediated antitumor effects during radiation. Science immunology 80 33963060
2020 Immunobiology and structural biology of AIM2 inflammasome. Molecular aspects of medicine 80 32660715
2019 AIM2 Inflammasome Assembly and Signaling. Advances in experimental medicine and biology 77 31628655
2020 AIM2 promotes the development of non-small cell lung cancer by modulating mitochondrial dynamics. Oncogene 76 32005973
2021 The Role of NLRP1, NLRP3, and AIM2 Inflammasomes in Psoriasis: Review. International journal of molecular sciences 70 34072753
2022 The AIM2 inflammasome: A novel biomarker and target in cardiovascular disease. Pharmacological research 69 36332811
2017 Tumor cell-specific AIM2 regulates growth and invasion of cutaneous squamous cell carcinoma. Oncotarget 67 28526809
2019 AIM2 promotes non-small-cell lung cancer cell growth through inflammasome-dependent pathway. Journal of cellular physiology 60 30953357
2021 AIM2 regulates anti-tumor immunity and is a viable therapeutic target for melanoma. The Journal of experimental medicine 59 34325468
2017 AIM2-Like Receptors Positively and Negatively Regulate the Interferon Response Induced by Cytosolic DNA. mBio 58 28679751
2021 AIM2 deletion enhances blood-brain barrier integrity in experimental ischemic stroke. CNS neuroscience & therapeutics 56 34156153
2016 The role of NLRP3 and AIM2 in inflammasome activation during Brucella abortus infection. Seminars in immunopathology 56 27405866
2014 HMGB1-DNA complex-induced autophagy limits AIM2 inflammasome activation through RAGE. Biochemical and biophysical research communications 56 24971542
2023 AIM2 promotes renal cell carcinoma progression and sunitinib resistance through FOXO3a-ACSL4 axis-regulated ferroptosis. International journal of biological sciences 55 36923928
2022 The DNA sensors AIM2 and IFI16 are SLE autoantigens that bind neutrophil extracellular traps. eLife 50 35608258
2014 Identification of Aim2 as a sensor for DNA vaccines. Journal of immunology (Baltimore, Md. : 1950) 50 25488991
2021 Blockade of AIM2 inflammasome or α1-AR ameliorates IL-1β release and macrophage-mediated immunosuppression induced by CAR-T treatment. Journal for immunotherapy of cancer 47 33414262
2024 Neutrophil extracellular traps promote acetaminophen-induced acute liver injury in mice via AIM2. Acta pharmacologica Sinica 46 38589685
2021 The complex role of AIM2 in autoimmune diseases and cancers. Immunity, inflammation and disease 44 34014039
2020 AIM2 Inflammasome's First Decade of Discovery: Focus on Oral Diseases. Frontiers in immunology 43 32903550
2020 Chronic cerebral hypoperfusion activates AIM2 and NLRP3 inflammasome. Brain research 42 32171704
2020 Aim2-mediated/IFN-β-independent regulation of gastric metaplastic lesions via CD8+ T cells. JCI insight 40 32053518
2018 Increased Levels of AIM2 and Circulating Mitochondrial DNA in Type 2 Diabetes. Iranian journal of immunology : IJI 40 29947343
2024 Ginsenoside Rg1 alleviates chronic inflammation-induced neuronal ferroptosis and cognitive impairments via regulation of AIM2 - Nrf2 signaling pathway. Journal of ethnopharmacology 38 38641079
2020 The Emerging Relevance of AIM2 in Liver Disease. International journal of molecular sciences 37 32906750
2023 Hematopoietic NLRP3 and AIM2 Inflammasomes Promote Diabetes-Accelerated Atherosclerosis, but Increased Necrosis Is Independent of Pyroptosis. Diabetes 34 37083999
2021 STAT3-mediated upregulation of the AIM2 DNA sensor links innate immunity with cell migration to promote epithelial tumourigenesis. Gut 33 34489308
2023 NLRP3 Attenuates Intraocular Inflammation by Inhibiting AIM2-Mediated Pyroptosis Through the Phosphorylated Salt-Inducible Kinase 1/Sterol Regulatory Element Binding Transcription Factor 1 Pathway. Arthritis & rheumatology (Hoboken, N.J.) 32 36529965
2023 Pristimerin suppresses AIM2 inflammasome by modulating AIM2-PYCARD/ASC stability via selective autophagy to alleviate tendinopathy. Autophagy 32 37647255
2020 Expression of AIM2 in Rheumatoid Arthritis and Its Role on Fibroblast-Like Synoviocytes. Mediators of inflammation 30 33162829
2022 Neutrophil extracellular traps promote keratinocyte inflammation via AIM2 inflammasome and AIM2-XIAP in psoriasis. Experimental dermatology 29 36401800
2020 CCL19 suppresses gastric cancer cell proliferation, migration, and invasion through the CCL19/CCR7/AIM2 pathway. Human cell 29 32564199
2022 Microglial AIM2 alleviates antiviral-related neuro-inflammation in mouse models of Parkinson's disease. Glia 28 35959803
2022 AIM2 upregulation promotes metastatic progression and PD-L1 expression in lung adenocarcinoma. Cancer science 28 36104978
2023 Exercise alleviates neovascular age-related macular degeneration by inhibiting AIM2 inflammasome in myeloid cells. Metabolism: clinical and experimental 27 37150437
2022 Re-Du-Ning injection ameliorates radiation-induced pneumonitis and fibrosis by inhibiting AIM2 inflammasome and epithelial-mesenchymal transition. Phytomedicine : international journal of phytotherapy and phytopharmacology 27 35665679
2020 AIM2 inhibits colorectal cancer cell proliferation and migration through suppression of Gli1. Aging 27 33291082
2017 Maturation-dependent expression of AIM2 in human B-cells. PloS one 27 28809949
2019 AIM2 deletion promotes neuroplasticity and spatial memory of mice. Brain research bulletin 26 31301379
2015 Deficient NLRP3 and AIM2 Inflammasome Function in Autoimmune NZB Mice. Journal of immunology (Baltimore, Md. : 1950) 26 26116505
2024 New insights into nucleic acid sensor AIM2: The potential benefit in targeted therapy for cancer. Pharmacological research 25 38272334
2024 AIM2 regulates autophagy to mitigate oxidative stress in aged mice with acute liver injury. Cell death discovery 25 38429284
2024 EIF2AK2 protein targeted activation of AIM2-mediated PANoptosis promotes sepsis-induced acute kidney injury. Renal failure 25 39311631
2023 AIM2 and Psoriasis. Frontiers in immunology 25 36742336
2024 Neutrophil extracellular traps facilitate liver inflammation/fibrosis progression by entering macrophages and triggering AIM2 inflammasome-dependent pyroptosis. Cell communication and signaling : CCS 24 39568027
2023 AIM2 inflammasome: A potential therapeutic target in ischemic stroke. Clinical immunology (Orlando, Fla.) 23 38142900
2021 USP21 Deubiquitinase Regulates AIM2 Inflammasome Activation. Journal of immunology (Baltimore, Md. : 1950) 23 34470856
2024 Bruceine A alleviates alcoholic liver disease by inhibiting AIM2 inflammasome activation via activating FXR. Phytomedicine : international journal of phytotherapy and phytopharmacology 21 38763006
2022 Absent in melanoma 2 (AIM2) in rheumatoid arthritis: novel molecular insights and implications. Cellular & molecular biology letters 21 36476420
2021 Nuclear AIM2-Like Receptors Drive Genotoxic Tissue Injury by Inhibiting DNA Repair. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 21 34658166
2016 AIM2 inhibits autophagy and IFN-β production during M. bovis infection. Oncotarget 21 27409673
2025 SIK2 mediated mitochondrial homeostasis in spinal cord injury: modulating oxidative stress and the AIM2 inflammasome via CRTC1/CREB signaling. Journal of neuroinflammation 20 41339921
2022 AIM2-inflammasome role in systemic lupus erythematous and rheumatoid arthritis. Autoimmunity 20 35880661
2023 Genomic DNA activates the AIM2 inflammasome and STING pathways to induce inflammation in lacrimal gland myoepithelial cells. The ocular surface 19 37769964
2024 Microglial mitochondrial DNA release contributes to neuroinflammation after intracerebral hemorrhage through activating AIM2 inflammasome. Experimental neurology 18 39278588
2023 Filament assembly underpins the double-stranded DNA specificity of AIM2-like receptors. Nucleic acids research 17 36864667
2023 The role of AIM2 in human hepatocellular carcinoma and its clinical significance. Pathology, research and practice 16 37060822
2023 Overexpressed CD44 is associated with B-cell activation via the HA-CD44-AIM2 pathway in lupus B cells. Clinical immunology (Orlando, Fla.) 16 37499961
2023 TRIM11 attenuates Treg cell differentiation by p62-selective autophagic degradation of AIM2. Cell reports 16 37804507
2023 Assembly mechanism of the inflammasome sensor AIM2 revealed by single molecule analysis. Nature communications 16 38042863
2022 Roles of AIM2 Gene and AIM2 Inflammasome in the Pathogenesis and Treatment of Psoriasis. Frontiers in genetics 16 36118867
2019 Expression and activity of AIM2-inflammasome in rheumatoid arthritis patients. Immunobiology 16 31836304
2024 The roles of AIM2 in neurodegenerative diseases: insights and therapeutic implications. Frontiers in immunology 15 39076969
2023 Inflammasomes NLRP3 and AIM2 in peri-implantitis: A cross-sectional study. Clinical oral implants research 15 37642257
2022 AIM2 inflammasome contributes to aldosterone-induced renal injury via endoplasmic reticulum stress. Clinical science (London, England : 1979) 15 34935888
2022 The P2X7R-NLRP3 and AIM2 Inflammasome Platforms Mark the Complexity/Severity of Viral or Metabolic Liver Damage. International journal of molecular sciences 15 35806450
2020 DROSHA-Dependent miRNA and AIM2 Inflammasome Activation in Idiopathic Pulmonary Fibrosis. International journal of molecular sciences 15 32121297
2019 Withaferin A modulates AIM2 inflammasome and caspase-1 expression in THP-1 polarized macrophages. Experimental cell research 15 31442452
2023 Impact of nsSNPs in human AIM2 and IFI16 gene: a comprehensive in silico analysis. Journal of biomolecular structure & dynamics 14 37139544
2023 Effects of AIM2 and IFI16 on Infectious Diseases and Inflammation. Viral immunology 14 37585649
2021 AIM2 Suppresses Inflammation and Epithelial Cell Proliferation during Glomerulonephritis. Journal of immunology (Baltimore, Md. : 1950) 14 34740957
2019 The absent in melanoma 2 (AIM2) inflammasome in microbial infection. Clinica chimica acta; international journal of clinical chemistry 14 30959045

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