Insights into IL-37, the role in autoimmune diseases

Xu, Wang‐Dong; Zhao, Yi; Liu, Yi

doi:10.1016/j.autrev.2015.08.006

Cited by 81 publications

(61 citation statements)

References 42 publications

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“…Now it is well documented that most of the biological effects of IL-37 are mediated by SIGIRR, whereas a subset of the effects are mediated by the ability of the nuclear IL-37 to engage SMAD-3; a member of the SMAD family that transduces TGF-b1-mediated signals. The SIGIRR KO mice show exacerbated responses in the mouse model of asthma as well as in experimental autoimmune encephalitis [75,76,83]. These observations strongly suggest the presence of a functional homologue for human IL-37 in mice.…”

Section: Il-37: a New Player In The Il-18/il-18bp Axismentioning

confidence: 81%

“…It is structurally related to IL-18, and the two cytokines together constitutes the IL-18 subfamily (reviewed in [75,76]). Both of the cytokines are targeted by IL-18BP.…”

Section: Il-37: a New Player In The Il-18/il-18bp Axismentioning

confidence: 99%

“…It inhibits LPS-induced production of several pro-inflammatory cytokines, and inhibits maturation of DC. The reduction of IL-37 synthesis by siRNA in human PBMCs leads to increased production of several proinflammatory cytokines e.g., IL-1a, IL-1b, IL-18, IL-6, IL-12, G-CSF, GM-CSF, and TNF-a [75,76]. The gene silencing in human intestinal and airways epithelial cells causes hyperactivation of NF-kB and an overproduction of proinflammatory cytokines.…”

Section: Il-37: a New Player In The Il-18/il-18bp Axismentioning

confidence: 99%

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Imbalanced production of IL-18 and its antagonist in human diseases, and its implications for HIV-1 infection

et al. 2016

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Section: Il-37: a New Player In The Il-18/il-18bp Axismentioning

confidence: 81%

“…It is structurally related to IL-18, and the two cytokines together constitutes the IL-18 subfamily (reviewed in [75,76]). Both of the cytokines are targeted by IL-18BP.…”

Section: Il-37: a New Player In The Il-18/il-18bp Axismentioning

confidence: 99%

Section: Il-37: a New Player In The Il-18/il-18bp Axismentioning

confidence: 99%

See 1 more Smart Citation

Imbalanced production of IL-18 and its antagonist in human diseases, and its implications for HIV-1 infection

et al. 2016

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“…In addition, IL-37 transgenic mice develop less severe colitis and psoriasis [55,56]. Based on the antiinflammatory activity of IL-37, several studies have been performed to investigate whether the administration of IL-37 may ameliorate chronic inflammation [57]. Studies performed in patients reported an overall increase of circulating as well as tissue IL-37 in inflammatory bowel disease [58], systemic lupus erythematosus [59], Graves' disease [60] and AS [61].…”

Section: Il-37mentioning

confidence: 99%

Cytokines in the pathogenesis of rheumatoid arthritis: new players and therapeutic targets

et al. 2017

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In recent years, the landscape of pro- and anti-inflammatory cytokines has rapidly expanded with the identification of new members proven to be involved at different extent in the pathogenesis of chronic immune mediated inflammatory diseases including rheumatoid arthritis (RA). The advance of our understanding of mediators involved in the pathogenesis of RA and in consequence, the development of novel targeted therapies is necessary to provide patients not responding to currently available strategies with novel compounds. The aim of this review article is to provide an overview on recently identified cytokines, emphasizing their pathogenic role and therapeutic potential in RA. A systematic literature review was performed to retrieve articles related to every cytokine discussed in the review. In some cases, evidence from animal models and RA patients is already consistent to move forward into drug development. In others, conflicting observation and the paucity of data require further investigations.Forty years after the discovery of IL-1, the landscape of cytokines is continuously expanding with increasing possibilities to develop novel therapeutic strategies in RA. Electronic supplementary material The online version of this article (10.1186/s41927-017-0001-8) contains supplementary material, which is available to authorized users.

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“…An increasing amount of evidence demonstrates that IL-37 plays an important role in regulating inflammatory and autoimmune diseases [14, 15], including psoriasis [11], obesity [16], dextran sulfate sodium (DSS)-induced colitis [17], liver inflammatory injury [18], rheumatoid arthritis [19] and myocardial ischemia/reperfusion injury [20]. Recently, IL-37 was found to attenuate atherosclerosis in ApoE -/- mice with diabetes [21]; however, the effect of IL-37 on the formation of atherosclerotic plaques in ApoE -/- mice and the underlying regulatory mechanisms of this process remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Transgenic Overexpression of IL-37 Protects Against Atherosclerosis and Strengthens Plaque Stability

Liu

Lin

et al. 2018

Cell Physiol Biochem

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Background/Aims: Recently, studies have shown that interleukin-37 (IL-37) is involved in atherosclerosis-related diseases. However, the regulatory mechanisms of IL-37 in atherosclerosis remain unknown. This study aims to determine the role of IL-37 in atherosclerosis and to investigate the underlying mechanisms involved. Methods: IL-37 expression in human atherosclerotic plaques was detected by immunohistochemical staining and real-time reverse transcription polymerase chain reaction (RT-PCR). Oil Red O staining was used to measure the size of plaques. Cell apoptosis in vitro and in vivo was tested by flow cytometric analysis and terminal deoxynucleotidyl-transferase mediated dUTP nick-end labeling (TUNEL) staining, respectively. Protein expression levels of IL-37, IL-18Rα and p-Smad3 were measured by Weston blotting. Results: Immunohistochemical staining revealed that IL-37 was highly expressed in human atherosclerotic plaques. Intracellular cytokine staining revealed that infiltrated CD4⁺ T lymphocytes and vascular smooth muscle cells (VSMCs), but not macrophages, were the major sources of IL-37. Mice that overexpressed IL-37 exhibited significant improvements in their atherosclerotic burden, as demonstrated by reduced plaque size, increased collagen levels, and reduced numbers of apoptotic cells in vivo. Subsequently, mechanistic studies showed that IL-37 played an anti-atherosclerotic role, at least partially, through reducing inflammation by promoting the differentiation of the T helper cell anti-inflammatory phenotype, and through increasing plaque stability by decreasing matrix metalloproteinase (MMP)-2/13-mediated degradation of collagen and inhibiting VSMCs apoptosis. Conclusion: IL-37 may be a novel potential therapeutic target in patients with atherosclerotic heart disease.

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Insights into IL-37, the role in autoimmune diseases

Cited by 81 publications

References 42 publications

Imbalanced production of IL-18 and its antagonist in human diseases, and its implications for HIV-1 infection

Imbalanced production of IL-18 and its antagonist in human diseases, and its implications for HIV-1 infection

Cytokines in the pathogenesis of rheumatoid arthritis: new players and therapeutic targets

Transgenic Overexpression of IL-37 Protects Against Atherosclerosis and Strengthens Plaque Stability

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