IL-1 family cytokines as drivers and inhibitors of trained immunity

Teufel, Lisa U.; Arts, Rob J. W.; Netea, Mihai G.; Dinarello, Charles A.; Joosten, Leo A. B.

doi:10.1016/j.cyto.2021.155773

Cited by 36 publications

(32 citation statements)

References 119 publications

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“…IL-1 family cytokines have been reported as drivers and inhibitors of trained immunity ( 101 ). Five IL-1 family cytokines promote trained immunity (TI) and four IL-1 family cytokines inhibit TI.…”

Section: Resultsmentioning

confidence: 99%

Aorta in Pathologies May Function as an Immune Organ by Upregulating Secretomes for Immune and Vascular Cell Activation, Differentiation and Trans-Differentiation—Early Secretomes may Serve as Drivers for Trained Immunity

Sun

et al. 2022

Front. Immunol.

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To determine whether aorta becomes immune organ in pathologies, we performed transcriptomic analyses of six types of secretomic genes (SGs) in aorta and vascular cells and made the following findings: 1) 53.7% out of 21,306 human protein genes are classified into six secretomes, namely, canonical, caspase 1, caspase 4, exosome, Weibel–Palade body, and autophagy; 2) Atherosclerosis (AS), chronic kidney disease (CKD) and abdominal aortic aneurysm (AAA) modulate six secretomes in aortas; and Middle East Respiratory Syndrome Coronavirus (MERS-CoV, COVID-19 homologous) infected endothelial cells (ECs) and angiotensin-II (Ang-II) treated vascular smooth muscle cells (VSMCs) modulate six secretomes; 3) AS aortas upregulate T and B cell immune SGs; CKD aortas upregulate SGs for cardiac hypertrophy, and hepatic fibrosis; and AAA aorta upregulate SGs for neuromuscular signaling and protein catabolism; 4) Ang-II induced AAA, canonical, caspase 4, and exosome SGs have two expression peaks of high (day 7)-low (day 14)-high (day 28) patterns; 5) Elastase induced AAA aortas have more inflammatory/immune pathways than that of Ang-II induced AAA aortas; 6) Most disease-upregulated cytokines in aorta may be secreted via canonical and exosome secretomes; 7) Canonical and caspase 1 SGs play roles at early MERS-CoV infected ECs whereas caspase 4 and exosome SGs play roles in late/chronic phases; and the early upregulated canonical and caspase 1 SGs may function as drivers for trained immunity (innate immune memory); 8) Venous ECs from arteriovenous fistula (AVF) upregulate SGs in five secretomes; and 9) Increased some of 101 trained immunity genes and decreased trained tolerance regulator IRG1 participate in upregulations of SGs in atherosclerotic, Ang-II induced AAA and CKD aortas, and MERS-CoV infected ECs, but less in SGs upregulated in AVF ECs. IL-1 family cytokines, HIF1α, SET7 and mTOR, ROS regulators NRF2 and NOX2 partially regulate trained immunity genes; and NRF2 plays roles in downregulating SGs more than that of NOX2 in upregulating SGs. These results provide novel insights on the roles of aorta as immune organ in upregulating secretomes and driving immune and vascular cell differentiations in COVID-19, cardiovascular diseases, inflammations, transplantations, autoimmune diseases and cancers.

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Section: Resultsmentioning

confidence: 99%

Aorta in Pathologies May Function as an Immune Organ by Upregulating Secretomes for Immune and Vascular Cell Activation, Differentiation and Trans-Differentiation—Early Secretomes may Serve as Drivers for Trained Immunity

Sun

et al. 2022

Front. Immunol.

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“…The IL-1 family members consist of seven agonists (IL-1 α (IL-1F1), IL-1 ß (IL-1F2), IL-18 (IL-1F4), IL-33 (IL-1F11), IL-36 α (IL-1F6), IL-36 ß (IL-1F8), and IL-36 γ (IL-1F9)), three antagonists (IL-Ra (IL-1F3), IL-36Ra (IL-1F5), and IL-38 (IL-1F10)) and an anti-inflammatory cytokine (IL-37 (IL-1F7)) in which the IL-1 has the axial role in innate immune system and inflammation modulation [ 2 , 128 , 129 , 135 , 136 ].…”

Section: Methods and Techniques For Determining Cytokinesmentioning

confidence: 99%

“…The occurrence of this immunomemory mechanism protects the individual against whether unrelated or homologous secondary infections. This process is known as trained immunity (TI) [ 135 , 161 ]. The term of TI was firstly described in 2011 [ 135 , 162 ].…”

Section: Methods and Techniques For Determining Cytokinesmentioning

confidence: 99%

“…This process is known as trained immunity (TI) [ 135 , 161 ]. The term of TI was firstly described in 2011 [ 135 , 162 ]. A wide range of compounds including endogenous molecules (e.g., fumarate, uric acid, oxidized low-density lipoprotein ((oxLDL) (the oxLDL directly stimulates the glycoproteins of TLR4, by which the expression of IL-1 ß increases), IL-1 ß , IFN γ (CD8 + cell derived)) [ 135 , 163 – 169 ], and exogenous microbial structures such as Bacillus Calmette-Guérin (BCG) (tuberculosis (TB)) vaccine, fungal ß -glucan (fungal cell wall constitution), and pathogenic protozoon of Plasmodium falciparum [ 135 , 170 – 172 ].…”

Section: Methods and Techniques For Determining Cytokinesmentioning

confidence: 99%

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The Interleukin-1 (IL-1) Superfamily Cytokines and Their Single Nucleotide Polymorphisms (SNPs)

Behzadi

Sameer

Nissar

et al. 2022

Journal of Immunology Research

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Interleukins (ILs)—which are important members of cytokines—consist of a vast group of molecules, including a wide range of immune mediators that contribute to the immunological responses of many cells and tissues. ILs are immune-glycoproteins, which directly contribute to the growth, activation, adhesion, differentiation, migration, proliferation, and maturation of immune cells; and subsequently, they are involved in the pro and anti-inflammatory responses of the body, by their interaction with a wide range of receptors. Due to the importance of immune system in different organisms, the genes belonging to immune elements, such as ILs, have been studied vigorously. The results of recent investigations showed that the genes pertaining to the immune system undergo progressive evolution with a constant rate. The occurrence of any mutation or polymorphism in IL genes may result in substantial changes in their biology and function and may be associated with a wide range of diseases and disorders. Among these abnormalities, single nucleotide polymorphisms (SNPs) can represent as important disruptive factors. The present review aims at concisely summarizing the current knowledge available on the occurrence, properties, role, and biological consequences of SNPs within the IL-1 family members.

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“…Other pro-inflammatory signalling nodes are also likely to play an important role in normoxic HIF induction, with NFkB and p42/44 mitogen-activated protein kinase (ERK) being examples of signalling nodes able to promote HIF-1α signalling [38][39][40]. Particularly important to mention here is the family of pro-inflammatory interleukin-1 (IL-1) cytokines, which are essential for innate immune responses and can signal via Akt, mTOR, ERK, and NFkB, and lead to increased HIF-1α activity [41]. Unsurprisingly, IL-1 signalling augments glycolysis in many cell lineages [42], and has wide-ranging HIF-dependent effects on myeloid cell function, as will be discussed later [41].…”

Section: Hypoxic Versus Normoxic Hypoxia Signalling In Myeloid Cellsmentioning

confidence: 99%

Hypoxia signalling in the regulation of innate immune training

Eades

Drozd

Cubbon

2021

Biochemical Society Transactions

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Innate immune function is shaped by prior exposures in a phenomenon often referred to as ‘memory’ or ‘training’. Diverse stimuli, ranging from pathogen-associated molecules to atherogenic lipoproteins, induce long-lasting training, impacting on future responses, even to distinct stimuli. It is now recognised that epigenetic modifications in innate immune cells, and their progenitors, underpin these sustained behavioural changes, and that rewired cellular metabolism plays a key role in facilitating such epigenetic marks. Oxygen is central to cellular metabolism, and cells exposed to hypoxia undergo profound metabolic rewiring. A central effector of these responses are the hypoxia inducible factors (or HIFs), which drive transcriptional programmes aiming to adapt cellular homeostasis, such as by increasing glycolysis. These metabolic shifts indirectly promote post-translational modification of the DNA-binding histone proteins, and also of DNA itself, which are retained even after cellular oxygen tension and metabolism normalise, chronically altering DNA accessibility and utilisation. Notably, the activity of HIFs can be induced in some normoxic circumstances, indicating their broad importance to cell biology, irrespective of oxygen tension. Some HIFs are implicated in innate immune training and hypoxia is present in many disease states, yet many questions remain about the association between hypoxia and training, both in health and disease. Moreover, it is now appreciated that cellular responses to hypoxia are mediated by non-HIF pathways, suggesting that other mechanisms of training may be possible. This review sets out to define what is already known about the topic, address gaps in our knowledge, and provide recommendations for future research.

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IL-1 family cytokines as drivers and inhibitors of trained immunity

Cited by 36 publications

References 119 publications

Aorta in Pathologies May Function as an Immune Organ by Upregulating Secretomes for Immune and Vascular Cell Activation, Differentiation and Trans-Differentiation—Early Secretomes may Serve as Drivers for Trained Immunity

Aorta in Pathologies May Function as an Immune Organ by Upregulating Secretomes for Immune and Vascular Cell Activation, Differentiation and Trans-Differentiation—Early Secretomes may Serve as Drivers for Trained Immunity

The Interleukin-1 (IL-1) Superfamily Cytokines and Their Single Nucleotide Polymorphisms (SNPs)

Hypoxia signalling in the regulation of innate immune training

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