ArticleCellular & molecular immunology2017
Common genetic heterogeneity of human interleukin-37 leads to functional variance.
Article in Cellular & molecular immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- A Critical Appraisal of the Diagnostic and Prognostic Utility of the Anti-Inflammatory Marker IL-37 in a Clinical Setting: A Case Study of Patients with Diabetes Type 2.International journal of environmental research and public health · 2023Article
- IL-37-a putative therapeutic agent in cardiovascular diseases.QJM : monthly journal of the Association of Physicians · 2022Review
- NLRP3 inflammasome triggers interleukin-37 release from human monocytes.European journal of immunology · 2022Article
- HomozygousProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Circulating Interleukin-37 Levels in Healthy Adult Humans - Establishing a Reference Range.Frontiers in immunology · 2021Article
- IL-1 Family Antagonists in Mouse and Human Skin Inflammation.Frontiers in immunology · 2021Review
- Parallel selection on ecologically relevant gene functions in the transcriptomes of highly diversifying salmonids.BMC genomics · 2019Article
- Potential role of IL-37 in atherosclerosis.Cytokine · 2019Review
- Cynomolgus macaque IL37 polymorphism and control of SIV infection.Scientific reports · 2019Article
- IL-37 isoform D downregulates pro-inflammatory cytokines expression in a Smad3-dependent manner.Cell death & disease · 2018Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin-37 (IL-37) is an inhibitory member of the IL-1 family of cytokines. We previously found that balanced selection maintains common variations of the human IL37 gene. However, the functional consequences of this selection have yet to be validated. Here, using cells expressing exogenous IL-37 variants, including IL-37 Ref and IL-37 Var1 and Var2, we found that the three variants of IL-37 exhibited different immunoregulatory potencies in response to immune stimulation. The protein level of IL-37 Var2 was found to be significantly less than that of IL-37 Ref or Var1, despite the comparable mRNA levels of all three variants. Further study showed that IL-37 Var2 was rapidly degraded by a proteasome-dependent mechanism mediated by enhanced polyubiquitination, leading to a transient upregulation of IL-37 Var2 after immune stimulation. Finally, when ectopically expressed in cells, human IL-37 Var2 exerted less inhibition on proinflammatory cytokine production than did other IL-37 variants. Conversely, purified extracellular IL-37 variant proteins demonstrated comparable inhibitory abilities in vitro. In conclusion, our study reveals that common genetic variants of IL37 lead to different immune-inhibitory potencies, primarily as a result of differences in IL-37 protein stability, suggesting the possible involvement of these variants in various human diseases.
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