Interleukin-33 in tissue homeostasis, injury, and inflammation

Molofsky, Ari B.; Savage, Adam K.; Locksley, Richard M.

doi:10.1016/j.immuni.2015.06.006

Cited by 638IL-33, ST2, and ILC PathwaysMast cells and histamineCytokine Signaling Pathways and Interactions

Interleukin-33 in tissue homeostasis, injury, and inflammation

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Molofsky, Ari B., Savage, Adam K., Locksley, Richard M.·2015·Immunity

DOI 10.1016/j.immuni.2015.06.006PMC PMC4471869

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Abstract

Interleukin-33 (IL-33) is a nuclear-associated cytokine of the IL-1 family originally described as a potent inducer of allergic type 2 immunity. IL-33 signals via the receptor ST2, which is highly expressed on group 2 innate lymphoid cells (ILC2s) and T helper 2 (Th2) cells, thus underpinning its association with helminth infection and allergic pathology. Recent studies have revealed ST2 expression on subsets of regulatory T cells, and for a role for IL-33 in tissue homeostasis and repair that suggests previously unrecognized interactions within these cellular networks. IL-33 can participate in pathologic fibrotic reactions, or, in the setting of microbial invasion, can cooperate with inflammatory cytokines to promote responses by cytotoxic NK cells, Th1 cells, and CD8(+) T cells. Here, we highlight the regulation and function of IL-33 and ST2 and review their roles in homeostasis, damage, and inflammation, suggesting a conceptual framework for future studies.

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The aging-related Oligo-3 cluster exhibited substantial upregulation of C4b and interleukin 33 (Il33).
“The aging-related cluster Oligo-3 exhibited substantial upregulation of C4b (Figure 2C), a complement protein of the innate immunity system, and interleukin 33 (Il33) (Figure 2C), a cytokine involved in inflammatory and innate immune response,39 consistent with previous results.17”
From Molecular and spatial signatures of mouse brain aging at single-cell resolution (2023) · cites this paper as [39]

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IL-33 Expands Suppressive CD11b+ Gr-1int and Regulatory T Cells, including ST2L+ Foxp3+ Cells, and Mediates Regulatory T Cell-Dependent Promotion of Cardiac Allograft Survival
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The Interleukin-33-p38 Kinase Axis Confers Memory T Helper 2 Cell Pathogenicity in the Airway
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IL‐33 synergizes with TCR and IL‐12 signaling to promote the effector function of CD8+ T cells
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Interleukin-1α
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IL-33-Mediated Protection against Experimental Cerebral Malaria Is Linked to Induction of Type 2 Innate Lymphoid Cells, M2 Macrophages and Regulatory T Cells
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Alarmin IL-33 Acts as an Immunoadjuvant to Enhance Antigen-Specific Tumor Immunity
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The biological paths of IL-1 family members IL-18 and IL-33
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Interleukin-33 ameliorates ischemic brain injury in experimental stroke through promoting Th2 response and suppressing Th17 response
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Common genetic variation at the IL1RL1 locus regulates IL-33/ST2 signaling
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IL-33 and Thymic Stromal Lymphopoietin Mediate Immune Pathology in Response to Chronic Airborne Allergen Exposure
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Expression of ST2, an Interleukin-1 Receptor Homologue, Is Induced by Proinflammatory Stimuli
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The role of basophils and proallergic cytokines, TSLP and IL-33, in cutaneously sensitized food allergy
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IL-1β suppresses innate IL-25 and IL-33 production and maintains helminth chronicity
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Transcriptional Regulation of Murine IL-33 by TLR and Non-TLR Agonists
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Visualization of IL-12/23p40 In Vivo Reveals Immunostimulatory Dendritic Cell Migrants that Promote Th1 Differentiation
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Epithelium: the interplay between innate and Th2 immunity
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Mechanisms of IL-33 processing and secretion: differences and similarities between IL-1 family members
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The Expression of ST2 Gene in Helper T Cells and the Binding of ST2 Protein to Myeloma-Derived RPMI8226 Cells
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Mast Cells Respond to Cell Injury through the Recognition of IL-33
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Negative regulatory receptors of the IL-1 family
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Interleukin-33 prolongs allograft survival during chronic cardiac rejection
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IL-33 Promotes Gastric Cancer Cell Invasion and Migration Via ST2–ERK1/2 Pathway
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IL-33 Receptor ST2 Amplifies the Expansion of NK Cells and Enhances Host Defense during Mouse Cytomegalovirus Infection
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Amplification of cytokine production through synergistic activation of NFAT and AP‐1 following stimulation of mast cells with antigen and IL‐33
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Interleukin 33: a switch-hitting cytokine
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Cutting Edge: IL-15-Independent NK Cell Response to Mouse Cytomegalovirus Infection
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Interleukin-33/ST2 axis promotes epithelial cell transformation and breast tumorigenesis via upregulation of COT activity
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Macrophage-Derived IL-33 Is a Critical Factor for Placental Growth
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IL-33 accelerates cutaneous wound healing involved in upregulation of alternatively activated macrophages.
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Crucial and Diverse Role of the Interleukin-33/ST2 Axis in Infectious Diseases
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Pronounced Phenotype in Activated Regulatory T Cells during a Chronic Helminth Infection
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Group 2 Innate Lymphoid Cells in Health and DiseasePreprint
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IL-33 mediates multi-walled carbon nanotube (MWCNT)-induced airway hyper-reactivity via the mobilization of innate helper cells in the lung
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Mechanical Stretch Suppresses microRNA-145 Expression by Activating Extracellular Signal-Regulated Kinase 1/2 and Upregulating Angiotensin-Converting Enzyme to Alter Vascular Smooth Muscle Cell Phenotype
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Identification of Constitutively Active Interleukin 33 (IL-33) Splice Variant
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Differential Expression of miR-145 in Children with Kawasaki Disease
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IL-33 Induces Nuocytes and Modulates Liver Injury in Viral Hepatitis
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The Alarmin IL-33 Is a Notch Target in Quiescent Endothelial Cells
Sundlisæter, E., Edelmann, R. J., Fosse, J. H., Sponheim, J., Küchler, A. M., Weiss, M., Udalova, I. A., Midwood, K. S., Kasprzycka, M., & Haraldsen, G. (2012) · American Journal Of Pathology · doi:10.1016/j.ajpath.2012.06.003 · Cited by 68 · see citing works
Epidermal Expression and Regulation of Interleukin-33 during Homeostasis and Inflammation: Strong Species Differences
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Expression Profiling of Aldh1l1-Precursors in the Developing Spinal Cord Reveals Glial Lineage-Specific Genes and Direct Sox9-Nfe2l1 Interactions
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Basophil modulation by cytokine instruction
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IL-33 Is Required for Disposal of Unnecessary Cells during Ovarian Atresia through Regulation of Autophagy and Macrophage Migration
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JAK2 is an important signal transducer in IL-33-induced NF-κB activation
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Modulation of IL ‐33/ ST 2 system in postinfarction heart failure: correlation with cardiac remodelling markers
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The mouse interleukin (Il)33 gene is expressed in a cell type- and stimulus-dependent manner from two alternative promoters
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MicroRNAs Are Essential for Stretch-induced Vascular Smooth Muscle Contractile Differentiation via MicroRNA (miR)-145-dependent Expression of L-type Calcium Channels
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I-L-C-2 it: type 2 immunity and group 2 innate lymphoid cells in homeostasis
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Unique Temporal and Spatial Expression Patterns of IL-33 in Ovaries during Ovulation and Estrous Cycle Are Associated with Ovarian Tissue Homeostasis
Carlock, C., Wu, J. G., Zhou, C., Tatum, K., Adams, H. P., Tan, F. K., & Lou, Y. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1400381 · Cited by 51 · see citing works
BCR-ABL–Induced Deregulation of the IL-33/ST2 Pathway in CD34(+) Progenitors from Chronic Myeloid Leukemia Patients
Levescot, A., Flamant, S., Basbous, S., Jacomet, F., Féraud, O., Bourgeois, E. A., Bonnet, M., Giraud, C., Roy, L., Barra, A., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-2797 · Cited by 51 · see citing works
Erratum: The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue–resident regulatory T cells
Vasanthakumar, A., Moro, K., Xin, A., Liao, Y., Gloury, R., Kawamoto, S., Fagarasan, S., Mielke, L. A., Afshar‐Sterle, S., Masters, S. L., et al. (2015) · Nature Immunology · doi:10.1038/ni0515-544d · Cited by 47 · see citing works
Serum amyloid A induces interleukin‐33 expression through an IRF7‐dependent pathway
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Participation of MyD88 and Interleukin-33 as Innate Drivers of Th2 Immunity to Trichinella spiralis
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Developmental expression of IL-33 in the mouse brain
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Astrocyte-derived interleukin-33 promotes microglial synapse engulfment and neural circuit development
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“The aging-related cluster Oligo-3 exhibited substantial upregulation of C4b (Figure 2C), a complement protein of the innate immunity system, and interleukin 33 ( Il33 ) (Figure 2C), a cytokine involved in inﬂammatory and innate immune response, 39 consistent with previous results.”
IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline
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., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1604032113 · Cited by 369 · see citing works
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ИСПОЛЬЗОВAНИЕ ПОТЕНЦИAЛA СОЦИAЛЬНЫХ ПAРТНЕРОВ В ПОДГОТОВКЕ БУДУЩИХ ПЕДAГОГОВ
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Authors: Molofsky, A. B., Savage, A. K., & Locksley, R. M.
Affiliations: University of California, San Francisco (US)
Howard Hughes Medical Institute (US)
Corresponding author: Locksley, Richard M.
ORCID: Molofsky, Ari B.
Savage, Adam K.
Locksley, Richard M.
Venue: Immunity
Publisher: Elsevier BV
Published: 2015-06
Volume: 42
Issue: 6
Pages: 1005-1019
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2015.06.006
PMC: PMC4471869
OpenAlex: W1490258901
Cited by: 638
References: 209
Citations by year: 2026: 48 · 2025: 40 · 2024: 54 · 2023: 42 · 2022: 65 · 2021: 78 · 2020: 86 · 2019: 55 · 2018: 53 · 2017: 58 · 2016: 52 · 2015: 6
FWCI: 5.32
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 381 d)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: Howard Hughes Medical Institute
National Heart, Lung, and Blood Institute (HL107202, P01HL107202, R01HL128903)
National Institute of Allergy and Infectious Diseases (R01AI030663, AI026918, R37AI026918, R01AI026918, AI030663)
National Institute of Diabetes and Digestive and Kidney Diseases (K08DK101604)
Topics: Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords: IL-33, ST2, tissue homeostasis, tissue repair, inflammation, Th2 immune response, allergic inflammation, helminthiasis, ILC2, Th2 cells, regulatory T cells, fibrosis, natural killer cells, Th1 cells, CD8+ T cells, cytokine regulation
MeSH terms: Interleukin-33, Interleukin-1 Receptor-Like 1 Protein, Animals, Cytotoxicity, Immunologic, Homeostasis, Humans, Immunity, Innate, Inflammation, Interleukins, Receptors, Cell Surface, Wounds and Injuries, Signal Transduction, Th2 Cells, T-Lymphocytes, Regulatory

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Interleukin-33 in tissue homeostasis, injury, and inflammation

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