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IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline
Open accessAbstract
Significance: Dysfunction of the innate immune system is involved in the pathogenesis of Alzheimer’s disease (AD); however, the pathophysiological mechanisms underlying these dysfunctions are unclear. Here we report that stimulation of IL-33/ST2 signaling rescues memory deficits and reduces the accumulation of β-amyloid in APP/PS1 mice that exhibit select pathologies associated with AD. Although impaired IL-33/ST2 signaling is associated with early progression of AD, IL-33 injection rescues contextual memory deficits and reduces the accumulation of β-amyloid in APP/PS1 mice. IL-33 skews the microglia toward an alternative activation state with enhanced Aβ phagocytic capacity and elevated antiinflammatory gene expression, which results in a decreased proinflammatory response in the brain. Thus, this study suggests that IL-33 can be developed as a new therapeutic intervention for AD.
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TL;DR
IL-33 administration reversed synaptic plasticity and contextual memory deficits and reduced amyloid pathology in APP/PS1 mice by enhancing microglial Aβ phagocytosis and shifting microglia/macrophages toward an antiinflammatory phenotype. The findings support IL-33/ST2 signaling as a potential therapeutic target in Alzheimer’s disease.
Key findings
- In 6- to 7-mo-old APP/PS1 mice, i.p. IL-33 (200 ng for 2 d) dramatically reversed impaired hippocampal LTP and restored contextual fear memory at 7 d after shock.
- IL-33 reduced soluble Aβ in cortices of 10-mo-old APP/PS1 mice by 54 ± 9% (n = 3 experiments); soluble Aβx-40 and Aβx-42 decreased by ∼50% and ∼30%, respectively. It also reduced 4G8-stained amyloid plaques in 12-mo-old APP/PS1 mice, and intracerebroventricular sST2 abolished this plaque reduction.
- IL-33 increased Aβ phagocytosis: methoxy-X04-labeled Aβ was detected in ∼33% of CD11b+ myeloid cells from APP/PS1 cortices, rising to ∼47% after IL-33; Aβ uptake by resident microglia increased by ∼80%, while infiltrating monocytes remained relatively stable.
- IL-33 increased antiinflammatory Arg1 and Fizz1 mRNA in CD11b+ myeloid cells and suppressed proinflammatory IL-1β, IL-6, and NLRP3 in APP/PS1 cortices; ST2-deficient microglia abolished IL-33-stimulated Aβ uptake.
Methods
- Mouse models: APP/PS1, 5XFAD, and St2−/− mice; WT C57BL/6 controls. In vivo IL-33 was given i.p. at 200 ng per mouse for 2 consecutive days, with some experiments using intracerebroventricular sST2 via osmotic pumps.
- Outcomes included hippocampal LTP at SC-CA1 synapses, open field habituation, contextual fear conditioning, soluble/insoluble Aβ by Western blot and ELISA, 4G8 plaque immunohistochemistry, microglial Aβ phagocytosis by flow cytometry, and inflammatory gene expression by ddPCR/qRT-PCR.
- Human data: serum sST2 measured in 17 healthy controls and 18 patients with MCI (Han Chinese, age ≥60 y), with clinical diagnosis by NINCDS-ADRDA criteria.
Limitations
- The paper does not include a dedicated limitations section; it states that whether IL-33/ST2 suppression of proinflammatory gene production via MyD88 competition mediates the observed effects “awaits further study,” and that further phenotypic characterization of the microglial subset with increased Aβ phagocytic capacity is needed.
- Evident from the text: the therapeutic evidence is primarily from transgenic mouse models, and the human data are limited to cross-sectional serum sST2 in small groups (17 controls, 18 MCI), not IL-33 treatment or clinical outcomes.
- Evident from the text: long-term safety, dosing durability, and whether the murine findings extrapolate to human AD are not established.
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46 Own result · 21 Own interpretation · 3 Not checked yet · 2 Own method
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“IL-33 injection further increased the proportion of CD11b + cells exhibiting methoxy-X04 fluorescence (∼47%; Fig. 3 F and G).”
§ IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline > Results
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-33 administration significantly increased Aβ phagocytic uptake by resident microglia by ∼80%, whereas the percentage of Aβ-containing infiltrating monocytes remained relatively stable (Fig. 3 H and I and SI Appendix, Fig. S8 E-G).”
§ IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline > Results
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- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“Specifically, soluble Aβ x-40 and Aβ x-42 species, which play major synaptotoxic roles in AD (21), were decreased by ∼50% and ∼30%, respectively, in the cortices of 10-mo-old IL-33-administered APP/PS1 mice (Fig. 2B).”
§ IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline > Results
plaindirectn = 3- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-33 administration reduces soluble Aβ levels and amyloid plaque deposition by promoting the recruitment and Aβ phagocytic activity of microglia; this is mediated by ST2/p38 signaling activation.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-33 administration increased CD68 expression in Iba1 + myeloid cells, that were in close contact with amyloid plaques (Fig. 3E).”
§ IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline > Results
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Serum levels of soluble ST2 (sST2), a decoy receptor for interleukin (IL)-33, increase in patients with mild cognitive impairment, suggesting that impaired IL-33/ST2 signaling may contribute to the pathogenesis of AD.”
- Also stated in: § Results · plain
“We found significantly higher levels of serum sST2, a decoy receptor of IL-33, in patients with mild cognitive impairment (MCI; with an increased risk of developing to AD in later life) compared with healthy controls (Fig. 1A);”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our 3D analysis confirmed the increased colocalization of myeloid cells and amyloid plaques in IL-33treated APP/PS1 mouse brains (Fig. 3 B and C), supporting the notion that IL-33 enhances the proximity between myeloid cells and amyloid plaques.”
§ IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline > Results
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice.”
- Also stated in: § Results · boosted
“An i.p. injection of recombinant IL-33 (200 ng) for 2 d dramatically reversed the LTP impairment of APP/PS1 mice (Fig. 1 B and C).”
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Results · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“IL-33 injection enhanced the recruitment of Iba1 + myeloid cells to amyloid plaques in these cortices (Fig. 3A).”
§ IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline > Results
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice.”
- Also stated in: § Results · plain
“IL-33 treatment was able to restore the impaired freezing response of the APP/PS1 mice at 7 d after the electric shock (Fig. 1G).”
- Also stated in: § Results · boosted
“Collectively, these results demonstrate that IL-33 can rescue the synaptic dysfunction and memory deficits of APP/PS1 mice.”
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Results · plain
- The quote only partly states this claim. 3
- It may state two separate claims as one. 6
- Probably not a substantial claim. 2
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“IL-33 rescues LTP impairment in APP/PS1 mutant mice.”
§ IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline > Statistical Analysis.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-33 ameliorates memory retrieval deficits of APP/PS1 mice in fear conditioning (FC) tests.”
§ IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline > Statistical Analysis.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“At the concentration used (200 ng i.p. daily for 2 d), IL-33 did not affect the general health or plasma histamine level in either WT or APP/PS1 mice (SI Appendix, Fig. S4).”
§ IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline > Results
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-33 ameliorates memory retrieval deficits of APP/PS1 mice in fear conditioning (FC) tests.”
§ IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline > Statistical Analysis.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Taken together, our results demonstrate that IL-33 administration mitigates the amyloid plaque pathology in APP/PS1 mice through the enhancement of Aβ phagocytosis by resident microglia and Aβ clearance, probably by increasing neprilysin levels.”
§ IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline > Results
hedgedconditional- Asserted: passes — The authors put it forward as true.
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“The investigators who performed the electrophysiological, immunohistochemical, RNA expression, and flow cytometry analyses and the behavioral tests were blinded to the genotypes of the mice and treatment conditions.”
§ IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline > Statistical Analysis.
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“IL-33 administration ameliorates synaptic impairment and behavioral deficits in APP/PS1 mice.”
§ IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline > Statistical Analysis.
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data suggest that IL-33 treatment reverses contextual memory deficits in APP/PS1 mice, probably through ameliorating the hippocampal synaptic dysfunctions.”
§ IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline > Results
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“IL-33 administration reduces soluble Aβ levels and Aβ plaques in APP/PS1 mice.”
§ IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline > Statistical Analysis.
plaindirectn = 6- Asserted: passes — The authors put it forward as true.
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In the paper
“The purity of microglia/infiltrating monocyte isolation was routinely >90% as determined by fluorescence staining for CD11b and flow cytometry analysis.”
§ IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline > Contextual Fear Conditioning.
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In the paper
“Furthermore, IL-33 treatment switches the microglia/macrophages to an alternative activation phenotype, resulting in a reduction of the proinflammatory response in the AD mouse brains.”
§ IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper relies on this without support.
There is no effective therapy for AD.
“There is no effective therapy for AD, in part because of our limited knowledge of its underlying pathophysiological mechanisms.”
The paper relies on this without support.
The mechanisms underlying the onset and progression of AD remain unclear.
“The mechanisms underlying the onset and progression of AD remain unclear.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Our results support previous studies showing improved behaviour in AD mouse models associated with enhanced microglial amyloid plaque phagocytosis in response to scanning ultrasound69, and treatment with IL-33 that signals exclusively via MyD8870.”
From Transcriptional signature in microglia associated with Aβ plaque phagocytosis (2021) · cites this paper as [70]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“CD45 is differentially expressed on microglia (CD45lo/CD11b+) and recruited myeloid cells (CD45hi/CD11b+), and this distinction is commonly used in flow cytometry experiments to distinguish recruited myeloid cells from resident microglia in various disease states [27, 40, 41].”
From IL-1β-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia (2019) · cites this paper as [27]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Furthermore, IL-33 administration ameliorated memory deficits and reduced Aβ deposition in the APP/PS1 mouse model (54).”
From The effect of Abi3 locus deletion on the progression of Alzheimer’s disease-related pathologies (2023) · cites this paper as [54]
The cited source says what the claim attributes to it.
In the citing paper
“Strikingly, activation of microglial cells by inflammatory molecules has been shown to enhance Aβ clearance by microglia [3, 26, 27].”
From IL-1β-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia (2019) · cites this paper as [27]
In the citing paper
“IL-33 ameliorated AD-associated phenotypes by promoting anti-inflammatory functions, which included induction of Arg1 (80).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [80]
Citations
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BackgroundNLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice
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Cited by
Sorted by citations
Items 201–300 of 370
The Role of the IL-33/ST2 Immune Pathway in Autoimmunity: New Insights and Perspectives
Ramezani, F. M., Babaie, F., Aslani, S., Hemmatzadeh, M., Mohammadi, F. S., Shabgah, A. G., Jadidi‐Niaragh, F., Ezzatifar, F., & Mohammadi, H. (2021) · Immunological Investigations · doi:10.1080/08820139.2021.1878212 · Cited by 17
“ulation of the innate immunity responses (Fu et al. 2016).”
BackgroundInfluentialXie, L., Sheehy, R. N., Muneer, A., Xiong, Y., Wrobel, J. A., Zhang, F., Park, K., Velez, J., Liu, J., Luo, Y., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-59128-z · Cited by 20
Roda, A. R., Montoliu‐Gaya, L., Serra-Mir, G., & Villegas, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186630 · Cited by 17
“IL-33 administration to APP/PS1 double-transgenic mouse model of AD could ameliorate cognitive impairment and reduce both Aβ40 and Aβ42 in the cortex [61].”
BackgroundLau, S., Wu, W., Seo, H., Fu, A. K. Y., & Ip, N. Y. (2021) · STAR Protocols · doi:10.1016/j.xpro.2020.100265 · Cited by 17
“For APP/PS1 mice, the proportion of Ab phagocytic microglia should be 10% and 20% at 12 and 16 months of age, respectively (Figure 2B) (Fu et al., 2016; Lau et al., 2020).”
BackgroundSelf-citationMicroglia, synaptic dynamics and forgetting
Wang, C., Wang, L., & Gu, Y. (2021) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2021.06.005 · Cited by 20
IL-33/ST2 Axis: A Potential Therapeutic Target in Neurodegenerative Diseases
Jia, Z., Guo, M., Ge, X., Chen, F., & Lei, P. (2023) · Biomolecules · doi:10.3390/biom13101494 · Cited by 17
“IL-33 can enable beta-amyloid (A β ) protein decreases and can activate the phagocytosis of microglia, thus playing a neuroprotective role [61].”
BackgroundAltered behavior in mice overexpressing soluble ST2
Kikuchi, M., Takase, K., Hayakawa, M., Hayakawa, H., Tominaga, S., & Ohmori, T. (2020) · Molecular Brain · doi:10.1186/s13041-020-00606-4 · Cited by 16
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“…enzyme USP17 and was significantly hypermethylated in the PTSD group, regulates the nuclear function and stability of interleukin 33 (Ni et al., 2015), which is highly expressed in the brain and known to have a critical role in the pathogenesis of Alzheimer’s disease (Fu et al., 2016).”
BackgroundHe, Z., Chen, Q., Wang, K., Lin, J., Peng, Y., Zhang, J., Yan, X., & Yan, J. (2024) · European Journal of Neuroscience · doi:10.1111/ejn.16242 · Cited by 18
“IL-33 drove the microglia to an antiinflammation phenotype and inhibited their expression of proinflammation genes (Fu et al., 2016).”
BackgroundInterleukin-33 regulates the functional state of microglia
Xiong, T., Wang, X., Zha, Y., & Wang, Y. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.1012968 · Cited by 18
“Following the identification of the requirement for ST2 receptor in microglia during Aβ phagocytosis (Fu et al., 2016), a molecular mechanism for microglial state transitions stimulated by IL-33 has recently been reported that IL-33 induces transcriptome reprogramming characterized by the restoration of homeostatic si…”
BackgroundInfluentialLi, S.-M., Liu, H., Qian, Y., Jiang, L., Liu, S., Liu, Y., Liu, C., & Gu, X. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109479 · Cited by 15
Emerging Roles of Microglia in Blood-Brain Barrier Integrity in Aging and Neurodegeneration
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“…ligand 1 (CX3CL1), to make microglia exhibit anti-inflammatory phenotype, but also promote the release of pro-inflammatory cytokines, leading to the breakdown of the BBB in vitro and inducing the activation of pro-inflammatory state of microglia, astrocytes, and endothelial cells [114-116].”
BackgroundWong, E., Malviya, M., Jain, T., Liao, G. P., Kehs, Z., Chang, J. C., Studer, L., Scheinberg, D. A., & Li, Y. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02474-z · Cited by 16
“It was previously shown that IL33 treatment ameliorates cognitive decline and amyloid burden in the AD model by activating microglia to increase A β phagocytic capacity and increase anti-in fl ammatory genes [53].”
IL‐33 as a Novel Serum Prognostic Marker of Intracerebral Hemorrhage
Miao, Y., Zhang, Z., Feng, X., & Sun, W. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/5597790 · Cited by 15
“IL-33 can reverse the synaptic plasticity damage and memory deficits in APP/PS1 mice, and its mechanism may be to promote the differentiation of microglia into an anti-inflammatory phenotype and reduce soluble Aβ levels and amyloid plaque deposition [30].”
BackgroundTherapeutic Manipulation of Ageing: Repurposing Old Dogs and Discovering New Tricks
Mallikarjun, V., & Swift, J. (2016) · EBioMedicine · doi:10.1016/j.ebiom.2016.11.020 · Cited by 14
“Importantly, while rapamycin has been shown to extend lifespan in a variety of pre-clinical models, the precise effects in mice have been shown to be sex-specific (Garratt et al., 2016; Miller et al., 2014) and specific to particular genetic backgrounds (Lamming et al., 2013, 2012).”
BackgroundThe Role of Astrocytes in Synaptic Dysfunction and Memory Deficits in Alzheimer’s Disease
de León-López, C. A. M., Navarro‐Lobato, I., & Khan, Z. U. (2025) · Biomolecules · doi:10.3390/biom15070910 · Cited by 19
Tan, Y. J., Siow, I., Saffari, S. E., Ting, S. K. S., Zeng, L., Kandiah, N., Tan, L. C. S., Tan, E., & Ng, A. S. L. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-221072 · Cited by 14
Guo, S., Qian, C., Li, W., Zeng, Z., Cai, J., & Luo, Y. (2023) · NeuroImmunoModulation · doi:10.1159/000533984 · Cited by 16
“…sclerosis and Alzheimer ’ s disease (AD), moderate levels of IL-33 can promote the polarization of microglia and Th cells toward anti-in fl ammatory phenotypes as microglia may effectively phagocytose harmful substances, leading to a reduction in nerve damage and disease progression [17, 27, 28].”
BackgroundInternalization of extracellular Tau oligomers in Alzheimer’s disease
Chinnathambi, S., Rangappa, N., & Chandrashekar, M. (2025) · Advances in clinical chemistry · doi:10.1016/bs.acc.2025.01.005 · Cited by 14
IL-33 and IL-10 Serum Levels Increase in MCI Patients Following Homotaurine Treatment
Toppi, E., Sireno, L., Lembo, M., Banaj, N., Messina, B., Golesorkhtafti, S., Spalletta, G., & Bossù, P. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.813951 · Cited by 14
“In particular, the alarmin IL-33 could ameliorate disease pathology and cognitive decline in AD animal models, possibly by promoting microglia capacity to phagocyte Ab and increasing anti-inflammatory gene expression (20).”
BackgroundThe role of IL-33 in depression: a systematic review and meta-analysis
Liu, R., Liu, L., Ren, S., Wei, C., Wang, Y., Li, D., & Zhang, W. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1242367 · Cited by 16
Interleukin-33 ameliorates perioperative neurocognitive disorders by modulating microglial state
Yang, D., Sun, Y., Lin, D., Li, S., Zhang, Y., Wu, A., & Wei, C. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.109982 · Cited by 15
Alt, C., Yuan, S., Wu, F., Stankovich, B. L., Calaoagan, J. M., Schopies, S., Wu, J. Y., Shen, J., Schneider, D., Zhu, Y., et al. (2019) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2019.05.030 · Cited by 13
Unravelling the therapeutic potential of IL-33 for atrophic AMD
Clare, A. J., Liu, J., Copland, D. A., Theodoropoulou, S., & Dick, A. D. (2021) · Eye · doi:10.1038/s41433-021-01725-5 · Cited by 12
Gaunt, J. R., Zainolabidin, N., Yip, A. K. K., Tan, J. M., Low, A. Y. T., Chen, A. I., & Ch’ng, T. H. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02913-8 · Cited by 12
IL-33/ST2 signaling pathway and Alzheimer's disease: A systematic review and meta-analysis
Jiang, T., Zheng, T., Li, W., Liu, N., & Wang, M. (2023) · Clinical Neurology and Neurosurgery · doi:10.1016/j.clineuro.2023.107773 · Cited by 12
Sládek, M., Houdek, P., Myung, J., Semenovykh, K., Dočkal, T., & Sumová, A. (2024) · Fluids and Barriers of the CNS · doi:10.1186/s12987-024-00547-3 · Cited by 12
“…33 ( Il33 ), which plays a role in reversing the buildup and preventing the new formation of amyloid plaques in animal AD model APP/PS1 mice [102], Lrp8os3 , coding for the receptor for AD genetic risk marker apolipoprotein E [103], or Fhl2 , coding adaptor protein physically inter-acting…”
BackgroundRefining the interactions between microglia and astrocytes in Alzheimer’s disease pathology
Chen, J., Xu, S., Wang, L., Liu, X., Liu, G., Tan, Q., Li, W., Zhang, S., & Du, Y. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.03.033 · Cited by 17
Chronic IL-21 drives neuroinflammation and promotes lipid accumulation in microglia
Oyamada, H. A. A., Ying, Y., Agrawal, S., Liu, A., Subramanian, V. S., Bento, C. A. M., & Agrawal, A. (2025) · Immunity & Ageing · doi:10.1186/s12979-025-00510-2 · Cited by 14
“Interestingly, its role in neurological diseases appears context-dependent, as IL-33 can be either protective or detrimental depending on the disease and underlying conditions [25–29].”
Chen, W.-W., Fu, W., Su, Y.-T., Fang, W., Fu, A. K. Y., & Ip, N. Y. (2019) · Scientific Reports · doi:10.1038/s41598-018-38103-3 · Cited by 12
Self-citationQian, F., He, R., Du, X., Wei, Y., Zhou, Z., Fan, J., & He, Y. (2024) · Neurochemical Research · doi:10.1007/s11064-024-04197-7 · Cited by 15
“…following tissue damage as an endogenous danger signal or “alarmin” [22], binding to the ST2 protein (the only well-documented receptor for IL-33) to play a complex immunomodulatory role in rodent models of neurological diseases, such as Alzheimer’s disease, multiple sclerosis, and stroke [23–25].”
InfluentialAljohani, N. B., Qusti, S. Y., Alsiny, M., Aljoud, F., Aljohani, N. B., Alsolami, E. S., Alamry, K. A., & Hussein, M. A. (2024) · RSC Advances · doi:10.1039/d4ra01965b · Cited by 11
Kaushal, S. K., Parul, P., Tripathi, A., Singh, D. P., Paul, A., Alka, K., Shukla, S., & Singh, D. R. (2024) · JBMR Plus · doi:10.1093/jbmrpl/ziae101 · Cited by 11
Sun, Y., Shi, X., Ohm, M., Körte, M., & Zagrebelsky, M. (2025) · Scientific Reports · doi:10.1038/s41598-025-95546-1 · Cited by 11
“…significantly polarized microglia toward an anti-inflammatory phenotype, reduced pro-inflammatory gene expression, and enhanced the phagocytic activity of microglia, thereby improving Aβ pathology in AD mice by promoting the recruitment of microglia and decreasing amyloid plaque deposition 67,68 .”
The role of innate lymphoid cells (ILCs) in mental health
Barichello, T. (2022) · Discover Mental Health · doi:10.1007/s44192-022-00006-1 · Cited by 11
“IL-33 improved Alzheimer’s disease-like pathology modulating IL-1β, IL-6, and NLR family pyrin domain containing 3 (NLRP3) genes in the cortices of APP/PS1 mice and decreasing cognitive impairment [39].”
BackgroundHua, J., Wang, F., Wei, X., Qin, Y., Lian, J., Wu, J., Ma, P., & Ma, X. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054317 · Cited by 11
“The toxicity of Aβ40 and metal-induced Aβ40 aggregates with or without MnPM toward neuronal pheochromocytoma (PC12) cells was tested by the MTT assay [50].”
MethodA Deep View of the Biological Property of Interleukin-33 and Its Dysfunction in the Gut
Wang, Y., He, C., Xin, S., Liu, X., Zhang, S., Qiao, B., Shang, H., Gao, L., & Xu, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241713504 · Cited by 12
Barbour, M., Wood, R., Hridi, S. U., Wilson, C., McKay, G., Bushell, T. J., & Jiang, H. (2018) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2018.02.012 · Cited by 11
“In support of this, genetic variants of IL-33 are associated with increased susceptibility to Alzheimer’s disease (AD) (Chapuis et al., 2009) whilst IL-33 administration has been shown to reverse synaptic plasticity and cognitive deficits in a mouse model of AD (Fu et al., 2016).”
InfluentialCross-regulation between the nervous system and type 2 immunity
Mroz, N. M., Chiaranunt, P., Molofsky, A. V., & Molofsky, A. B. (2025) · Science Immunology · doi:10.1126/sciimmunol.adp6450 · Cited by 12
Lee, J., Mizuno, K., Watanabe, H., Lee, I., Tsumita, T., Hida, K., Yawaka, Y., Kitagawa, Y., Hasebe, A., Iimura, T., et al. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03192-7 · Cited by 14
“The inefficient phagocytic activity of microglia with aging may lead to the formation of Aβ plaques, neuronal dystrophy characterized by tau accumulation, and neuroinflammation, which collectively represent the core pathologies of AD [25, 26].”
BackgroundPerceiving traumatic brain injury from glymphatic system
Yang, Z., Li, P., & Wei, J. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03126-6 · Cited by 13
Zhong, X., Liu, M.-Y., He, M., Du, K., & Wei, M. (2017) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s138073 · Cited by 10
“13,14 To investigate whether rs11792633 or rs7044343 polymorphism in IL-33 produced a marked effect in mediating susceptibility to AD, several case–control studies had evaluated the role of the IL-33 gene in AD.”
Nandi, S., Alviña, K., Lituma, P. J., Castillo, P. E., & Hébert, J. M. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.11.017 · Cited by 10
“…much attention, less is known about what regulates developmentally generated DGCs. Growth factor signaling has been implicated in neurodevelopmental, neurodegenerative, and psychiatric disorders (Dode et al., 2003; Dubourg et al., 2016; Fu et al., 2016; Lu et al., 2013; Turner et al., 2012).”
Li, Q., Zhao, Y., Shi, C., & Song, X. (2022) · Brain Sciences · doi:10.3390/brainsci12091244 · Cited by 10
“As research on IL-33 has progressed, it has been shown to be expressed in microglia, neurons and oligodendrocytes [18].”
BackgroundMethodResultInfluentialZhu, Y., Fang, C., Zhang, Q., Lu, Y., Zhang, R., Wang, A., Bu, X., Zhang, J., Ju, Z., Zhang, Y., et al. (2021) · BMC Geriatrics · doi:10.1186/s12877-021-02288-6 · Cited by 10
IL-33/ST2 Signaling Regulates Synaptic Plasticity and Homeostasis in the Adult Hippocampal Circuitry
Wang, Y., Fu, A. K. Y., & Ip, N. Y. (2021) · DNA and Cell Biology · doi:10.1089/dna.2021.0491 · Cited by 10
“Concordantly, IL-33/ST2 signaling dysfunction is implicated in the progression of several neurological disorders such as AD (Chapuis et al. , 2009; Allan et al. , 2016; Fu et al. , 2016; Liew et al. , 2016).”
Self-citationArosio, B., Rossi, P. D., Ferri, E., Consorti, E., Ciccone, S., Lucchi, T. A., & Montano, N. (2025) · Experimental Gerontology · doi:10.1016/j.exger.2025.112692 · Cited by 9
“It is important to note that several cytokines, including IL-1 β , promote microglial activation and mediate A β clearance (Fu et al., 2016; Shaftel et al., 2007), supporting the dual role of activated microglia in the pathogenesis of AD, namely the beneficial one consisting of phagocytosis and the…”
Chen, T., Chen, J., Guo, M., Liu, Y., Wang, J., Fang, Y., Chen, Y., & Zhang, A. (2025) · Neuropharmacology · doi:10.1016/j.neuropharm.2025.110336 · Cited by 10
Sha, S., Chaigneau, T., & Krantic, S. M. (2023) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2023.04.005 · Cited by 10
“…Cavanagh et al., 2016 and reviewed in Mango et al., 2019) similar attenuation of LTP has been reported in a variety of additional AD-like mouse models (i.e. APP/PS1dE9: Fu et al., 2016; Oliveira et al., 2021; 5xFAD: Hwang et al., 2017; Forner et al., 2021; hAβ-KI: Baglietto-Vargas et al., 2021).”
ResultFunctional bioengineered tissue models of neurodegenerative diseases
Mullis, A. S., & Kaplan, D. L. (2023) · Biomaterials · doi:10.1016/j.biomaterials.2023.122143 · Cited by 10
Beneficial Upshots of Naturally Occurring Antioxidant Compounds against Neurological Disorders
Saha, S., Sadhukhan, P., & Sil, P. C. (2017) · Wiley eBooks · doi:10.1002/9783527803781.ch3 · Cited by 9
Wan, W., Wang, Y., Wang, Y., et al. (2023) · Biochemical Genetics · doi:10.1007/s10528-023-10503-9 · Cited by 8
“Chronic deposition of amyloid-beta (Aβ) and neuronal loss in the brain are considered as the primary neuropathological hallmarks of AD (Peng et al. 2016; Fu et al. 2016).”
Zhang, F., Yang, W., Sun, R., Duan, X., 杨云华, Wang, A., & Tian, Y. (2025) · Antioxidants and Redox Signaling · doi:10.1177/15230864251401591 · Cited by 13
“IL-33 can promote the recruitment and phagocytosis of microglia by upregulating ST2, thereby reducing the load of soluble A b and amyloid plaques in AD (Fu et al., 2016; Jia et al., 2023).”
Breast cancer in schizophrenia could be interleukin-33-mediated
Borovčanin, M., & Vesić, K. (2021) · World Journal of Psychiatry · doi:10.5498/wjp.v11.i11.1065 · Cited by 8
IL-33/ST2 drives inflammatory pain via CCL2 signaling and activation of TRPV1 and TRPM8
Wang, L., Zhang, J., Qiu, S., Huang, R., Wang, Y., Wang, Y., Li, M., Ye, Q., Zhang, S., Qi, Z., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-08119-3 · Cited by 8
Irisin ameliorates obesity and insulin resistance via adipose tissue IL-33 and regulatory T cells
Mu, A., Wang, G., Zammit, N. W., Roth, L., Maierhaba, Y., Laznik-Bogoslavski, D., Cai, C., Langston, P. K., Zhang, Q., Afonina, I. S., et al. (2026) · Nature Metabolism · doi:10.1038/s42255-026-01491-2 · Cited by 10
“Moderate increases in IL-33 levels reversed memory deficits in APP/PS1 mice (an Alzheimer’s disease mouse model), whereas administration of IL-33 in wild-type mice induced neuroin-flammation that further led to impaired memory 60,61 .”
Wen, C., Li, Z., Li, C., Zheng, J., Wang, P., Chen, L., You, Q., & Ding, L. (2024) · Fitoterapia · doi:10.1016/j.fitote.2024.105823 · Cited by 7
Dissecting the immune response of CD4+ T cells in Alzheimer’s disease
Kostić, M. S., Živković, N., Cvetanović, A., Bašić, J., & Stojanović, I. R. (2024) · Reviews in the Neurosciences · doi:10.1515/revneuro-2024-0090 · Cited by 8
Wang, X., Ke, Y., Cao, Z., Fu, Y., Cheng, Y., Liu, D., Chen, H., Guo, K., Li, Y., Yang, M., et al. (2024) · BMC Cardiovascular Disorders · doi:10.1186/s12872-024-04274-3 · Cited by 9
“Exogenous recombinant IL33 can significantly inhibit the expression of proinflammatory genes in the brains of Alzheimer’s disease model mice, contribute to neuroprotection, and improve hippocampal synaptic dysfunction and cognitive impairment [32].”
Nishizaki, T. (2017) · Neural Plasticity · doi:10.1155/2017/2531453 · Cited by 7
“Intriguingly, IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 double-transgenic mice, an animal AD model [12].”
BackgroundGrubman, A., Choo, X. Y., Chew, G., Ouyang, J. F., Sun, G., Croft, N. P., Rossello, F. J., Simmons, R., Buckberry, S., Landin, D. V., et al. (2019) · doi:10.1101/639054 · Cited by 7
Carvalho, D. B., Díaz‐Amarilla, P., Dapueto, R., Santi, M. D., Duarte, P., Savio, E., Engler, H., Abin‐Carriquiry, J. A., & Arredondo, F. (2023) · Journal of Molecular Neuroscience · doi:10.1007/s12031-023-02105-2 · Cited by 7
“Moreover, it has a role in injury healing and has been found neuroprotective in multiple models by regulating microglia and astrocyte phenotype (Gadani et al. 2015; Fu et al. 2016; Yang et al. 2017; Carlock et al. 2017; Chen et al. 2019c).”
BackgroundMulti-Target-Directed Ligand Approach in Anti-Alzheimer’s Drug Discovery
Patil, V. M., Masand, N., Gautam, V., Kaushik, S., & Wu, D. H. (2023) · Springer eBooks · doi:10.1007/978-981-99-2657-2_13 · Cited by 9
Ho, G. J., Lam, L. Q., Tran, T. T., Wei, J., & Hashimoto, M. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1430593 · Cited by 7
Chen, H., Chang, X., Zhou, J., Zhang, G., Cheng, J., Zhang, Z., Xing, J., Yan, C., & Liu, Z. (2025) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/0118715273337232241121113048 · Cited by 6
Exogenous pericyte delivery protects the mouse kidney from chronic ischemic injury
Song, T., Zhu, X., Eirin, A., Jiang, Y., Krier, J. D., Tang, H. R., Jordan, K. L., Lerman, A., & Lerman, L. O. (2022) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00064.2022 · Cited by 6
CCR5 regulates Aβ1-42-induced learning and memory deficits in mice
Huang, H.-Y., Salinas, S., Cornell, J. L., Udoh, I.-B., Shen, Y., & Zhou, M. (2024) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2024.107890 · Cited by 7
Microglia as a Possible Alternative Therapeutic for Dementia
Alavez-Rubio, J. S., & Juárez‐Cedillo, T. (2024) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-230112 · Cited by 6
The role of the gut microbiome in the regulation of astrocytes in Alzheimer's disease
Chandra, S., & Vassar, R. J. (2024) · Neurotherapeutics · doi:10.1016/j.neurot.2024.e00425 · Cited by 7
The role of IL-1 family of cytokines in the pathogenesis and therapy of Alzheimer’s disease
Li, C., Zhang, X., Wang, Y., Cheng, L., Li, C., & Yu, X. (2024) · Inflammopharmacology · doi:10.1007/s10787-024-01534-8 · Cited by 6
“Ultimately, these effects contribute to the improvement of AD progression (Fu et al. 2016a, b).”
Soluble expression and purification of bioactive interleukin 33 in E. coli
Do, B. H., Park, S., Kwon, G. G., Nguyen, M. T., Kang, H. J., Song, J.-A., Yoo, J., Nguyen, A. N., Jang, J., Jang, M., et al. (2017) · Biotechnology and Bioprocess Engineering · doi:10.1007/s12257-017-0060-0 · Cited by 7
“In the central nervous system, IL-33 activates macrophages [8] and the administration of IL-33 can reduce soluble Aβ levels and amyloid plaque deposition by promoting phagocytosis by microglia [9].”
Gou, L.-L., Yue, G. G., Chan, B. C.-L., et al. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.156596 · Cited by 5
Ai, H., Zhang, S., Si, C., Liu, T., Zheng, X., Tian, X., & Bai, W. (2025) · Behavioral and Brain Functions · doi:10.1186/s12993-025-00285-y · Cited by 7
Shen, C., Liu, Z., Chen, F., Zhu, X., Fan, G., Ning, P., Li, Q., Zhang, X., Dong, H., Liu, Y., et al. (2025) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.07.010 · Cited by 6
Jia, Z.-X., Guo, M., Li, M., Liao, P., Yan, B., Zhang, W., Cheng, F.-Y., Liu, Y., Zhang, Z.-H., Wei, C., et al. (2025) · Military Medical Research · doi:10.1186/s40779-025-00631-1 · Cited by 7
Astrocytes phenomics as new druggable targets in healthy aging and Alzheimer’s disease progression
Lana, D., Ugolini, F., Iovino, L., Attorre, S., & Giovannini, M. G. (2025) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1512985 · Cited by 6
“These and other strategies such as the use of IL-33 to APP/PS1 mice with improvement of cognitive functions (Fu et al., 2016), although promising, require further investigation.”
Mitchener, V. F. T., Thackray, M. J., & Arancibia‐Cárcamo, I. L. (2025) · The Journal of Physiology · doi:10.1113/jp287015 · Cited by 8
“For example, IL-33 administration in an APP/PS1 mouse model of AD reduced A β levels by enhancing microglial phagocytosis, with no effect on synapse elimination (Fu et al., 2016).”
Role of Interleukin33 in Rejuvenation of Aged Neurons and Age-Related Dementias
Lou, Y. (2021) · Neuroscience Insights · doi:10.1177/26331055211030251 · Cited by 5
Can soluble ST2 be a new marker in heart failure?
Konukoğlu, D. (2017) · International journal of medical biochemistry/International journal of medical biochemistry : · doi:10.14744/ijmb.2017.36844 · Cited by 5
1st International Conference on Human & Translational Immunology
Hope, J. L., Pulendran, B., Schoenberger, S. P., & Katsikis, P. D. (2016) · Nature Immunology · doi:10.1038/ni.3635 · Cited by 5
Single-nucleus multiome analysis of human cerebellum in Alzheimer’s disease-related dementiaPreprint
Cheng, F., Feng, Y., Flanagan, M. E., Bonakdarpour, B., Jamshidi, P., Castellani, R. J., Mao, Q., Chu, X., Gao, H., Liu, Y., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-4871032/v1 · Cited by 5
The Role of Biomarkers in Predicting Cognitive Impairment in Elderly Patients with Heart Failure
Arslan, A. (2024) · Turk Kardiyoloji Dernegi Arsivi-Archives of the Turkish Society of Cardiology · doi:10.5543/tkda.2024.97143 · Cited by 5
“15 However, we did not find a correlation between sST2 levels and cognitive dysfunction in patients aged 65 and older with HFrEF.”
BackgroundLong-term prognostic importance of high levels of sST2 in patient with AMI: a meta-analysis
Ji, H. (2024) · American Journal of Translational Research · doi:10.62347/haql3794 · Cited by 4
“Additionally, sST2 plays a role in extracellular matrix, inflammation, inde - pendent of IL-33 pathway [31, 32].”
BackgroundGuo, R., 中国科学院合肥物质科学研究院, 中., Xie, W., Yu, B., Song, C., Ji, X., Wang, X., Zhang, M., Zhang, X., 中国科学技术大学研究生院科学岛分院, 安. 合. 2., et al. (2024) · 动物学研究 · doi:10.24272/j.issn.2095-8137.2024.034 · Cited by 8
Bando, K., Tanaka, Y., Winias, S., Sugawara, S., Mizoguchi, I., & Endo, Y. (2023) · Inflammation Research · doi:10.1007/s00011-023-01699-y · Cited by 4
“2–1 μg IL-33 reportedly attenuates cancer [58], sepsis [59], and Alzheimer’s disease-like pathology [60].”
BackgroundMicroRNA and Alzheimer’s disease: Diagnostic biomarkers and potential therapeutic targets
Huang, Y., Chen, Y., He, Z., Lu, W., Lai, H., Wang, Y., & Wang, J. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-25-00002 · Cited by 4
“…been found to reverse synaptic plasticity impairments and memory deficits in APP/PS1 transgenic mice; this finding has been linked to a reduction in soluble Aβ levels and amyloid plaque deposition, likely due to the promotion of microglial recruitment and enhanced Aβ phagocytosis (Fu et al., 2016).”
Huang, R., Lin, B.-B., Lu, Z., Hao, Y., Li, C. F., Lin, Z., Zhang, Y., Wei, N., & Chen, J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1770509 · Cited by 5
Reducing decoys focuses fighting microglia
Duggan, M. R., & Walker, K. A. (2022) · Nature Aging · doi:10.1038/s43587-022-00251-7 · Cited by 3
IL-33 deficiency inhibits Toxoplasma gondii infection by promoting NLRP3 inflammasome
Chen, Y., He, X., Chen, Y., et al. (2024) · Parasitology Research · doi:10.1007/s00436-024-08414-8 · Cited by 3
“…IL-33 attenuated TLR4 expression and NF-κB activation with decreased Th1 cytokine and increased Th2 cytokines (Peng et al. 2018; Ryffel et al. 2019; Lamberet et al. 2020), and it also drove type-2 innate lymphoid cell expansion and M2 macrophage polarization (Besnard et al. 2015; Fu et al. 2016).”
Wang, H., Cheng, Z., Xu, Z., Wang, M., Sun, X., Liu, W., Wang, J., Yang, Q., Zhang, T., Song, J., et al. (2025) · Brain and Behavior · doi:10.1002/brb3.70478 · Cited by 3
Liu, T., & Li, X. (2025) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.70460 · Cited by 3
“Moreover, in the brains of APP/PS1 mice, injecting IL ‐ 33 changed the innate immune response by shifting M1 macrophages into an M2 anti ‐ inflammatory phenotype and decreasing the levels of pro ‐ inflammatory cytokines, including IL ‐ 1 β and IL ‐ 6 [136].”
Toscano, E. C. D. B., Lessa, J. M. K., de Oliveira, G. N. D., Gonçalves, A. P. D. F., Vieira, É., Rachid, M., & Teixeira, A. (2020) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2020.107351 · Cited by 2
ST2 levels and neurodegenerative diseases: is this a significant relation?
Arora, H., Javed, B., Kutikuppala, L. V. S., Chaurasia, M., Khullar, K., Kannan, S., & Varshitha, G. (2024) · Annals of Medicine and Surgery · doi:10.1097/ms9.0000000000001939 · Cited by 3
“In autoimmune disease, the IL-33/ST2 axis can increase pro-in fl ammatory cytokine release; however, in some metabolic diseases, such as type 1 diabetes, IL-33 can be considered an anti-in fl ammatory cytokine [56] .”
BackgroundFriend or foe? Targeting microglia in Alzheimer’s disease
Dhib-Jalbut, S. S. (2016) · Cytokine · doi:10.1016/j.cyto.2016.06.027 · Cited by 3
“In a recent publication in PNAS by Fu and colleagues [5], the authors reported on the potential involvement of IL-33 in the pathogenesis of AD using the APP/PS1 double transgenic mouse model.”
BackgroundImpact of wildfire smoke and diesel exhaust on inflammatory response in aging human microgliaPreprint
Cuní‐López, C., Ng, M. F., Stewart, R., Milton, L. A., Etebar, F., Sun, Y., Vivian, E. R., Nguyen, T. H., Asare, P. F., Lupton, M. K., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.20.629570 · Cited by 4
Acharya, V., Fan, K.-H., Snitz, B. E., Ganguli, M., DeKosky, S. T., López, O. L., Feingold, E., & Kamboh, M. I. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26146940 · Cited by 2
“Mouse models of AD have shown that IL-33/IL1RL1 signaling can alleviate cognitive impairment in AD by activating microglia to phagocytize amyloid beta [41].”
Xu, Y., Wu, T., Lo, L. T., Ko, C., Wang, X., & Ma, C. H. E. (2025) · Advanced Science · doi:10.1002/advs.202505421 · Cited by 2
Evaluation of Retinal Vascularity Index in Patients with COVID-19: A Case–Control Study
Zhou, S. W., Shrivastav, A., Gilada, T., Ng, X. L., Ng, S. P., Chua, C. H., Dutt, S., Natarajan, S., & Agrawal, R. V. (2022) · Ophthalmology and Therapy · doi:10.1007/s40123-022-00630-8 · Cited by 2
“These have been shown to promote anti-inflammatory microglial response in murine models [23].”
BackgroundHuang, L., Fu, C., Liao, S., & Long, Y. (2024) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2024.07.008 · Cited by 3
“Fu et al. reported that IL-33 treatment modulated the innate immune response through polarizing microglia to an anti-inflammatory phenotype (M2) and reducing proinflammatory gene expression in APP/PS1 mice (Fu et al., 2016).”
BackgroundWang, P., Hu, J., Chen, C., Jiang, Z., Zhang, Y., Lin, K., Liao, L., & Wang, X. (2024) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2024.111194 · Cited by 2
Metadata
- Authors
- Fu, A. K. Y., Hung, K.-W., Yuen, M. Y. F., Zhou, X., Mak, D. S. Y., Chan, I. C. W., Cheung, T. H., Zhang, B., Fu, W.-Y., Liew, F. Y., & Ip, N. Y.
- Affiliations
- Hong Kong University of Science and Technology (HK)
- Second Affiliated Hospital of Zhejiang University (CN)
- Soochow University (CN)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-04-18
- Volume
- 113
- Issue
- 19
- Pages
- E2705-13
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4868478
- OpenAlex
- W2342031861
- Semantic Scholar
- 1eac3f908af98105c0179fde2edb52b24e9f5d0c
- Cited by
- 369
- References
- 61
- Citations by year
- 2026: 18 · 2025: 41 · 2024: 45 · 2023: 39 · 2022: 33 · 2021: 48 · 2020: 40 · 2019: 24 · 2018: 35 · 2017: 31 · 2016: 14
- FWCI
- 27.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- IL-33, Alzheimer's disease, soluble ST2, amyloid-beta, microglial activation, innate immunity, synaptic plasticity, memory impairment, APP/PS1 mice, amyloid plaques, p38 MAPK signaling, microglial polarization, neuroinflammation, NLRP3 inflammasome, IL-1β, interleukin-6
- MeSH terms
- Interleukin-33, Alzheimer Disease, Animals, Brain, Cognition Disorders, Female, Male, Mice, Transgenic, Cytokines, Treatment Outcome, Neuroprotective Agents, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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