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The Interleukin-1 Family: Back to the Future
Open accessAbstract
Interleukin-1 (IL-1) is a central mediator of innate immunity and inflammation. The IL-1 family includes seven ligands with agonist activity (IL-1α and IL-1β, IL-18, IL-33, IL-36α, IL-36β, IL-36γ), three receptor antagonists (IL-1Ra, IL-36Ra, IL-38), and an anti-inflammatory cytokine (IL-37). Members of the IL-1 Receptor (IL-1R) family include six receptor chains forming four signaling receptor complexes, two decoy receptors (IL-1R2, IL-18BP), and two negative regulators (TIR8 or SIGIRR, IL-1RAcPb). A tight regulation via receptor antagonists, decoy receptors, and signaling inhibitors ensures a balance between amplification of innate immunity and uncontrolled inflammation. All cells of the innate immune system express and/or are affected by IL-1 family members. Moreover, IL-1 family members play a key role in the differentiation and function of polarized innate and adaptive lymphoid cells. Here we will review the key properties of IL-1 family members, with emphasis on pathways of negative regulation and orchestration of innate and adaptive immunity.
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“In addition, NLRP3 inflammasome activation reduces phagocytosis of Aβ by microglial cells, thus increasing the Aβ depositions and contributing to the pathogenesis of AD (Garlanda et al., 2013; Gold and El Khoury, 2015).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Garlanda et al., 2013
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“Interleukin-18 is a member of the large interleukin-1 family40 that has recently been associated with cytokine storm disorders.”
From Cytokine storm (2020) · cites this paper as [40]
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“IL-18 was initially identified and described as an IFN-c–inducing factor for its ability to enhance IFN-c production by T cells and natural killer (NK) cells, particularly in conjunction with IL-12 (23,24).”
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“The family contains seven ligands with agonistic (IL-1a, IL-1b, IL-18, IL-33, IL-36a, IL-36b, and IL-36g), three ligands with antagonistic (IL-1Ra, IL-36Ra, and IL-38), and one ligand with antiinflammatory activity (IL-37) (3, 4).”
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“IL1R8 (also known as TIR8 or single Ig IL1-related receptor, SIGIRR) is a member of the interleukin-1 receptor (IL1R) family acting as a negative regulatory receptor (13).”
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“The binding actions of CD121a account for IL-1 mediated inflammation and pathology [48,49]; loss of IL-1 signaling in CD121a−/− mice attenuates the formation of acellular capillaries in diabetic retina [50] and infiltration of pro-inflammatory leukocytes into ischemic tissue [51].”
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“In this context, members of the IL1 cytokines family are chief regulators of innate immunity and inflammation (38).”
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“Nevertheless, the inactivation of IL-33, the inhibition of its receptor, or using its soluble “decoy” receptor lead to important anti-inflammatory effects [31].”
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Understanding Inflammasomes and PD-1/PD-L1 Crosstalk to Improve Cancer Treatment Efficiency
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“Its expression can be induced by IL-1β, TLR stimulation and TGFβ [32,33,36,37].”
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“IL-1β and IL-18 are produced by infiltrating hematopoietic cells, such as dendritic cells (DC) and macrophages, in mouse kidneys [57].”
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“Toll-like receptors (TLRs)(3) and Interleukin-1 (IL-1) receptors perform critical roles in innate immune and inflammatory responses (1, 2).”
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“IL-18 is considered an inflammasome product whose main function is to promote IFN-g secretion (39).”
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“IL-1α is one marker of innate activation [19].”
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“To note, pro-IL-1α (also expressed after the autocrine stimulation of IL-1RI, (Di Paolo and Shayakhmetov, 2016)), unlike pro-IL-1β, acts as a transcription factor via nuclear translocation (Gabay et al., 2010; Weber et al., 2010).”
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“The cytokine IL-1β is a “master regulator” of inflammation by regulating various processes of the innate immune system (Garlanda et al., 2013).”
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CXCL8 , MMP12 , and MMP13 are common biomarkers of periodontitis and oral squamous cell carcinoma
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The cytokine/chemokine response in Leishmania/HIV infection and co-infection
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Extracorporeal Photopheresis Promotes IL-1β Production
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“IL-1b is a key immunostimulatory molecule belonging, along with IL-1a, IL-18, IL-36, and IL-37, to the IL-1 family (36).”
BackgroundStaphylococcus aureus Induces Shedding of IL-1RII in Monocytes and Neutrophils
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“Il1rn encodes the IL-1 receptor antagonist, IL-1RA, that acts as a negative regulator of IL-1β activity [32].”
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“role in the regulation of acute and chronic inflammation as an immune response amplifier.(31) IL-10 suppresses the immune response through several methods, including pro-”
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“3 Introduction Interleukin-1 (IL-1), a critical regulator of inflammation and pro-inflammatory cytokine of the IL-1 superfamily, has long been known to play a role in inflammatory syndromes, autoimmune diseases, and cancers [1-6].”
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“Introduction Interleukin-1β (IL-1β) is a potent proinflammatory cytokine capable of inducing various inflammatory responses in various cell types [1, 2].”
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“Previous tissue expression analyses showed that SIGIRR widely distributes in various tissues examined (2, 50).”
Background
Metadata
- Authors
- Garlanda, C., Dinarello, C. A., & Mantovani, A.
- Affiliations
- Radboud University Medical Center (NL)
- University of Milan (IT)
- Corresponding author
- Mantovani, Alberto
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 39
- Issue
- 6
- Pages
- 1003-1018
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC3933951
- OpenAlex
- W2145866317
- Cited by
- 1,945
- References
- 151
- Citations by year
- 2026: 80 · 2025: 118 · 2024: 136 · 2023: 122 · 2022: 168 · 2021: 172 · 2020: 202 · 2019: 165 · 2018: 194 · 2017: 192 · 2016: 171 · 2015: 156 · 2014: 66 · 2013: 1
- FWCI
- 11.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- European Research Council
- Associazione Italiana per la Ricerca sul Cancro
- National Institutes of Health (A115614, AR-45584)
- European Commission (FP7-HEALTH-2011- ADITEC 280873)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- interleukin-1 family, innate immunity, inflammation, IL-1 receptor family, interleukin-1 receptor antagonist, decoy receptor, IL-18, IL-33, IL-36, IL-37, IL-38, IL1RAP, SIGIRR, negative regulation of cytokine signaling, lymphocyte differentiation, innate and adaptive immunity
- MeSH terms
- Animals, Gene Expression Regulation, Humans, Immunity, Innate, Interleukin-1, Interleukins, Ligands, Receptors, Interleukin-1, Adaptive Immunity
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