Monocytes and dendritic cells are the primary sources of interleukin 37 in human immune cells

Rudloff, Ina; Cho, Steven; Lao, Jason C.; Ngo, Devi; McKenzie, Matthew; Nold-Petry, Claudia A.; Nold, Marcel F.

doi:10.1189/jlb.3ma0616-287r

Cited by 52 publications

(55 citation statements)

References 62 publications

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“…The difference in results between our results and the previous experiments published by Ballak et al [15] may be due to differences in methods to monitor food intake. In addition, non-littermates were used in the first experiment in this paper and in the study by Ballak et al [12]. Therefore, the reduction in fat mass and metabolic phenotype that were found initially could also be due to differences in genetic make-up or composition of gut microbiota [24,25].…”

Section: Discussionmentioning

confidence: 99%

“…The first studies into the function of IL-37 showed that it is a natural suppressor of innate inflammatory and immune responses [10]. In humans, several tissues and cell types express IL-37, including blood monocytes [11,12], epithelial cells [13], endothelial cells [14] and, importantly, also adipocytes [9,15]. IL-37 mRNA is degraded in the absence of inflammation, but upon lipopolysaccharide (LPS) stimulation, that is, a pro-inflammatory stimulus, IL-37 expression increases [16,17,18].…”

Section: Introductionmentioning

confidence: 99%

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IL-37 Expression Reduces Lean Body Mass in Mice by Reducing Food Intake

Kuipers

Ballak

Wit

et al. 2018

IJMS

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The human cytokine interleukin (IL)-37 is an anti-inflammatory member of the IL-1 family of cytokines. Transgenic expression of IL-37 in mice protects them from diet-induced obesity and associated metabolic complications including dyslipidemia, inflammation and insulin resistance. The precise mechanism of action leading to these beneficial metabolic effects is not entirely known. Therefore, we aimed to assess in detail the effect of transgenic IL-37 expression on energy balance, including food intake and energy expenditure. Feeding homozygous IL-37 transgenic mice and wild-type (WT) control mice a high-fat diet (HFD; 45% kcal palm fat) for 6 weeks showed that IL-37 reduced body weight related to a marked decrease in food intake. Subsequent mechanistic studies in mice with heterozygous IL-37 expression versus WT littermates, fed the HFD for 18 weeks, confirmed that IL-37 reduces food intake, which led to a decrease in lean body mass, but did not reduce fat mass and plasma lipid levels or alterations in energy expenditure independent of lean body mass. Taken together, this suggests that IL-37 reduces lean body mass by reducing food intake.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

IL-37 Expression Reduces Lean Body Mass in Mice by Reducing Food Intake

Kuipers

Ballak

Wit

et al. 2018

IJMS

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“…The primers used for amplifying the IL-10 were: forward 5′-GCC TAA CAT GCT TCG AGA TC-3′; reverse 5′-TGA TGT CTG GGT CTT GGT TC–3′ [21]; IL-37: forward 5′-TCA GCT GAA GAA GGA GAA ACT G-3′; reverse 5′-TTA TCT GTC ACC CCA ACA GG-3′ [22]. …”

Section: Methodsmentioning

confidence: 99%

Rapid Identification of Genome-Edited Mesenchymal Stem Cell Colonies via Cas9

et al. 2019

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Mesenchymal stem cells (MSCs) have been intensively investigated and widely applied in regenerative medicine and immune modulation. However, their efficacy declines during the aging or disease process. Thus, genome-edited MSCs with over-expression or inhibition of specific genes hold a great deal of promise in terms of their therapeutic application. Here we optimized the direct PCR approach for rapid identification of genome-edited MSCs with only ten cells required, which reduces the time and labor to expand the MSC colonies. Combined with our previously optimized guide RNA structure and plasmid construction strategy for Cas9, we successfully identified MSC colonies over-expressing IL-10 in the AAVS1 locus.

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“…IL-37 has not been widely studied, perhaps because its mouse homologue is still unidentified [18]. Its expression is relatively low in human cells under physiological conditions, but monocytes are the main producers of IL-37 within human peripheral blood mononuclear cells (PBMCs) [19]. Both IL-37 precursor (pro-IL-37) and processed forms (mIL-37) are biologically active, although the mIL-37 monomer has higher anti-inflammatory potency [20].…”

Section: Introductionmentioning

confidence: 99%

Priming is dispensable for NLRP3 inflammasome activation in human monocytes

Gritsenko¹,

Martín-Sánchez³

et al. 2020

Preprint

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Interleukin (IL)-1 family of cytokines modulate immune responses during infection and inflammation. IL-18 and IL-1β are members of the IL-1 family, which contribute to inflammatory conditions such as rheumatoid arthritis and Alzheimer's disease. and IL-1β are produced as inactive precursors that are activated by large macromolecular complexes called inflammasomes upon sensing damage or pathogenic signals. Canonical NLRP3 inflammasome activation is regarded to require a priming step that causes NLRP3 and IL-1β gene upregulation, and also NLRP3 posttranslational licencing. A subsequent activation step leads to the assembly of the inflammasome and the cleavage of pro-IL-18 and pro-IL-1β by caspase-1 into their mature forms, allowing their release. Here we show that in primary human monocytes, the initial priming step is dispensable to form an active NLRP3 inflammasome. We found that, in the absence of priming, the NLRP3 activator nigericin caused the processing and release of constitutively expressed IL-18. Another IL-1 family member, IL-37, is constitutively cleaved but the release of its mature form was mediated by inflammasome activation, also in the absence of a priming step. This NLRP3 activation was characterised by ASC oligomerisation as well as caspase-1 and GSDMD cleavage and was blocked by the NLRP3 inhibitor MCC950 and in NLRP3 deficient cells. IL-18 and IL-37 release were impaired in GSDMD deficient THP-1s, suggesting 2 that pyroptosis is required for release of these cytokines. This work highlights the readiness of the NLRP3 inflammasome to assemble in the absence of priming and hence contribute to sterile inflammatory processes in health and disease. Significance StatementThe NLRP3 inflammasome is a driver of inflammation through the processing of Interleukins (IL)-1β and IL-18. Human monocytes coordinate the innate immune response through inflammasome activation following exposure to pathogens and damage signals. We currently think of NLRP3 activation as a 2 step process: priming (NLRP3 gene upregulation and post-translational licencing) and assembly. Here we show that the priming step is dispensable for NLRP3 inflammasome activation in human monocytes. The second signal alone is sufficient for caspase-1 activation, leading to cell death and the release of the constitutively expressed IL-18 and mIL-37.This reveals that in human monocytes, the NLRP3 inflammasome is already licenced and able to quickly assemble to mount an inflammatory response.

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Monocytes and dendritic cells are the primary sources of interleukin 37 in human immune cells

Cited by 52 publications

References 62 publications

IL-37 Expression Reduces Lean Body Mass in Mice by Reducing Food Intake

IL-37 Expression Reduces Lean Body Mass in Mice by Reducing Food Intake

Rapid Identification of Genome-Edited Mesenchymal Stem Cell Colonies via Cas9

Priming is dispensable for NLRP3 inflammasome activation in human monocytes

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