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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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Written from the paper’s full text.
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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 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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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 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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- Load-bearing: passes — The paper’s conclusions depend on it.
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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
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 · 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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- Load-bearing: passes — The paper’s conclusions depend on it.
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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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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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.
- Checkable: passes — It can be checked against evidence.
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The quote only partly states this claim.
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 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.
- Checkable: passes — It can be checked against evidence.
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The quote only partly states this claim.
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
“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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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
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 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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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The quote only partly states this 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
“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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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
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In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- 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
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- 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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It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
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.
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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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]
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杨榕 (2012) · 福建艺术
Chen, H., Chang, X., Zhou, J., Zhang, G., Cheng, J., Zhang, Z., Liu, Z., & Yan, C. (2021) · Research Square · doi:10.21203/rs.3.rs-1043837/v1
“Microglia are the rst responder to Aβ accumulation and its activation can initiate an in ammatory response by producing a large number of in ammatory molecules including TNF-α, IL-6, IL-1β, iNOS and COX2, which result in synaptic degeneration, neuronal cell death, and cognitive dysfunction [32].”
BackgroundRole of IL-33/ST2 Axis in Chronic Inflammatory Neurological Disorderss
Dimitrijević, J., Arsenijević, A., Milovanović, M., Stojanović, B., Arsenijević, D., Milovanović, J., & Arsenijević, N. (2021) · Serbian Journal of Experimental and Clinical Research · doi:10.2478/sjecr-2020-0038
“lowing applications of recombined IL-33 to transgenic APP/PS1 mice that spontaneously develop Alzheimer’s disease like pathology, it was observed that IL-33 promotes activation of microglia and macrophages in the direction of the M2 anti-inflammatory phenotype, thereby enhancing the phagocytic activity of microglia (1…”
BackgroundPasterkamp, R. J., & Raj, D. D. A. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.732629163.793546117
Obulesu, M. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816412-9.00006-9
Wang, Z., Li, Q., Wu, W., Lu, Y., Wen, J., Ren, J., Zhao, H., & Zuo, Z. (2020) · Research Square · doi:10.21203/rs.3.rs-125098/v1
Kano, M., & Watanabe, T. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.732629163.793562678
Lou, Y. (2022) · American Journal of Biomedical Science & Research · doi:10.34297/ajbsr.2022.15.002170
Ding, B., Lin, C., Liu, Q., He, Y., Ruganzu, J. B., Jin, H. Z., Peng, X., Ji, S., Ma, Y., & Yang, W. (2020) · Figshare · doi:10.6084/m9.figshare.13093892
Glia Maturation Factor Beta: A Novel Neuro-Impairment Prediction Factor in Toxoplasmosis
Matini, M., Amini, R., & Foroughi-Parvar, F. (2024) · Iranian Journal of Public Health · doi:10.18502/ijph.v53i5.15602
“Interleukin 33 (IL33), as a candidate orchestra of immune cells, is involved in the pathology of brain tissue damage including, stroke (12, 13), neuro-degeneration (14, 15), experimental autoimmune encephalomyelitis (EAE) (16, 17), and central nervous system (CNS) infection.”
BackgroundExploring the Association between Oral Microbiome and Mild Cognitive Impairment: A Narrative Review
Tonkaboni, A., Sayyari, M., Khodadadzadeh, P., Khorshidi, S., Golalipour, S., & Haghighi, L. (2024) · Advances in Alzheimer s Disease · doi:10.4236/aad.2024.132003
In vivo and in vitro assays, and safety profiles of cannabinoids
Gwedela, M. N. V., Jana, C. E., Mwambyale, T., Chikowe, I., Chimphepo, L., & Chirambo, G. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95927-8.00009-8
Liu, B., & Liu, S. (2025) · Theoretical and Natural Science · doi:10.54254/2753-8818/2024.19400
IL_33 as a Modulator of Neuroinflammation in Alzheimer’s disease: An ELISA Approach
Th, S., Sh, I., & Kismat, T. (2024) · Al-Turath Medical Journal · doi:10.63964/atmj.2024.1.1
Raghuvanshi, S., Mazumder, A., & Das, S. (2025) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/0118715273378092250623064748
An, H., Gu, J., & Li, T. (2025) · Brain and Behavior · doi:10.1002/brb3.70797 · Cited by 1
Microglial plasticity across development mediates infantile amnesiaPreprint
Stewart, E., Zielke, L. G., Guillaume, G., Boer, A. D., Power, S. D., & Ryan, T. J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.17.683060
Xie, M., Diao, Y., Zhang, J., Hao, M., Wang, Z., Tan, R., Ma, J., Hu, X., Hao, Z., & Zhu, T. (2025) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2025.578800
Bailey, C. S., Gant, J. C., Frazier, H. N., Morganti, J. M., Coleman, M. J., Davis, V. A., Vekaria, H. J., Sullivan, P. G., Norris, C. M., Eldik, L. J. V., et al. (2025) · GeroScience · doi:10.1007/s11357-025-01948-4
“This interpretation better accords with reports that IL-33 improves hippocampal-dependent spatial memory (30, 31) and elevated levels are associated with reduced neuropathology in some contexts (32–35).”
Lope‐Piedrafita, S., Serra-Mir, G., Melón, P., Bonaterra‐Pastra, A., Hernández‐Guillamón, M., & Villegas, S. (2025) · Biomolecules · doi:10.3390/biom15111602 · Cited by 1
“An increase in TNF α (U = 0; p = 0.0022; r = 1) and IL-6 (U = 1; p = 0.0043; r = 0.94), and a reduction in the anti-inflammatory IL-33 [44] (U = 0; p = 0.0022; r = 1) levels were found.”
InfluentialBenítez, D. P., Jiang, S., Wood, J. I., Wang, R., Hall, C. M., Peerboom, C., Wong, N., Stringer, K. M., Vitanova, K. S., Smith, V. C., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14992873
Reverchon, F., de Concini, V., Larrigaldie, V., Benmerzoug, S., Briault, S., Togbe, D., Ryffel, B., Quesniaux, V. F. J., & Menuet, A. (2020) · Figshare · doi:10.6084/m9.figshare.12947651
Benítez, D. P., Jiang, S., Wood, J. I., Wang, R., Hall, C. M., Peerboom, C., Wong, N., Stringer, K. M., Vitanova, K. S., Smith, V. C., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14992879
Benítez, D. P., Jiang, S., Wood, J. I., Wang, R., Hall, C. M., Peerboom, C., Wong, N., Stringer, K. M., Vitanova, K. S., Smith, V. C., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14992870
Kong, F., Jiang, X., Wang, R., Zhai, S., Zhang, Y., & Wang, D. (2020) · Figshare · doi:10.6084/m9.figshare.13101031
Benítez, D. P., Jiang, S., Wood, J. I., Wang, R., Hall, C. M., Peerboom, C., Wong, N., Stringer, K. M., Vitanova, K. S., Smith, V. C., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14992882
Benítez, D. P., Jiang, S., Wood, J. I., Wang, R., Hall, C. M., Peerboom, C., Wong, N., Stringer, K. M., Vitanova, K. S., Smith, V. C., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14992876
Zhu, Y., Fang, C., Zhang, Q., Lu, Y., Zhang, R., Wang, A., Bu, X., Zhang, J., Ju, Z., Zhang, Y., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14670172
Reverchon, F., de Concini, V., Larrigaldie, V., Benmerzoug, S., Briault, S., Togbe, D., Ryffel, B., Quesniaux, V. F. J., & Menuet, A. (2020) · Figshare · doi:10.6084/m9.figshare.12947654
Benítez, D. P., Jiang, S., Wood, J. I., Wang, R., Hall, C. M., Peerboom, C., Wong, N., Stringer, K. M., Vitanova, K. S., Smith, V. C., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14992867
Riluzole shifts glial responses to protect synapses and memory in Aβ oligomer–treated ratsPreprint
Wint-Mon, M.-K., Kida, H., Kimura, R., & Mitsushima, D. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.26.696626
Nedeljkovic, J., Milovanović, J., Marković, V., Solovjova, N., Mijailovic, S. S., Zdravkovic, N. D., Nedeljkovic, N., & Milovanovic, M. (2026) · Biomedicines · doi:10.3390/biomedicines14020459 · Cited by 1
“…due to significantly greater neuronal loss in the cortex and hippocampus [14], while exogenous IL-33 treatment in Amyloid Precursor Protein (APP)/Presenilin 1 (PSEN1) transgenic mice enhances A β clearance and shifts microglial polarization toward a restorative, anti-inflammatory phenotype [15].”
The regulatory effects of circulating normal immunoglobulins on autophagy and Th17 response
Das, M. (2017) · theses.fr (ABES) · doi:10.70675/ea6bb914zc789z45bez864fz4c3386135691 · Cited by 2
Dalamaga, Μ. (2026) · Metabolism Open · doi:10.1016/j.metop.2026.100466
“Notably, moderate IL-33 administration has been shown to improve memory and reverse cognitive deficits in Alzheimer's disease mouse models by promoting microglial A β clearance, reducing amyloid burden, and polarizing microglia toward anti-inflammatory phenotypes [39].”
Dually Charged Dendrimeric Polyglycerol Modulates Interleukin-33 at Alarmin Receptors in Microglia
Zhang, I., Herrmann, A., Mohammadifar, E., Herre, F., Multhaup, G., Haag, R., & Maysinger, D. (2026) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.6c00161
Luteolin inhibits IL-33/ST2L-induced M2 macrophage polarization in endometriosis
Wang, W., Chen, Y. C., Wang, W., Jiang, L., Bai, D., Yang, Y. F., Wang, H., Wang, M., Si, H., Long, J., et al. (2026) · Molecular Immunology · doi:10.1016/j.molimm.2026.05.008
Arosio, B., Ferri, E., Rossi, P. D., Aiello, J., Caponetto, S., Olivieri, F., Fenoglio, C., Galimberti, D., Lucchi, T. A., & Montano, N. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1831919
Wong, D. Y. K., Fu, W., Uhm, H., Jiang, Y., Yip, Y. C. C., Mok, V., Kwok, T. C. Y., Ouyang, L., Fu, A. K. Y., & Ip, N. Y. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2536489123
“Given that IL - 33 signaling regulates microglial interactions with A β (17, 19, 20), we examined the characteristics of microglia in the cortices of trazodone - treated APP/PS1 mice.”
Self-citationPiłat, D., Baranger, K., & Rivera, S. (2026) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2026.07.004
Gong, M., Lan, J. X., & Miao, J. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1908574 · Cited by 3
“IL-33, derived in part from astrocytic and related glial programs, promotes microglial synaptic engulfment during development but can also rescue A β -induced cognitive and synaptic deficits in APP/PS1 mice (Fu et al., 2016; Vainchtein et al., 2018).”
Riluzole shifts glial responses to protect synapses and memory in Aβ oligomer–treated rats
Min-Kaung-Wint-Mon, Kida, H., Kimura, R., & Mitsushima, D. (2026) · Journal of Neuroinflammation · doi:10.1186/s12974-026-03972-3
“For example, astrocyte-derived interleukin-33 enhances microglial Aβ phagocytosis, while A2 polarization is associated with upregulation of Aβ-degrading enzymes such as neprilysin and scavenger receptors including CD36 [75, 78].”
Roy, S., Mandal, M., Banerjee, M., Madbhagat, P., Chande, A. G., & Ukil, A. (2026) · The Journal of Immunology · doi:10.1093/jimmun/vkag246
Gao, M., Li, M., Wei, H., An, W., Luo, J., Wang, Z., Wei, H., & Xiao, F. (2026) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2026.179328
Ma, Y., Zhang, T., Yu, T., Chen, Q., Su, S., Lin, Y., Shi, J., Zou, Y., Li, S., Liu, S., et al. (2026) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2026.122434
Frisch, C., Baker, L., Srinivasan, G., Mintah, A. E., Leyasi, S., Pedroza, M., Galyon, B., & Brafman, D. A. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1856154
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
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