IL-37 Mediation of Inflammation and Immune Response

Interleukin 37 (IL-37) is a fundamental anti-inflammatory cytokine within the IL-1 family. Synthesis of IL-37 is induced in immune and non-immune cells following inflammatory stimuli. Intracellularly, pro-IL-37 is cleaved by caspase-1 into its mature form, which binds to the transcription factor Smad3 and translocates to the nucleus to suppress the gene expression of pro-inflammatory mediators. Extracellularly, IL-37 forms a complex with IL-18 receptor α and the co-receptor IL-1R8 (formerly SIGIRR), thereby attenuating signal cascades such as NF-κB and p38 MAPK. The net effect is a broad suppression of innate and adaptive immune responses, including down-regulation of tumour necrosis factor α, interleukin 6 and interleukin 1β, modulation of macrophage polarisation and inhibition of inflammasome activation. These properties have translated into protective roles in models of atherosclerosis, autoimmunity, metabolic disorders and oncology. IL-37 also promotes regulatory T cell expansion and dendritic cell tolerogenicity, highlighting its potential as a therapeutic target and biomarker in inflammatory and immune-mediated diseases.

Research from Nature Portfolio

Studies have illuminated the therapeutic potential of IL-37 in cardiovascular disease. In a foundational investigation, exogenous administration of human IL-37 in ApoE-deficient mice significantly reduced aortic plaque burden and enhanced plaque stability. IL-37 treatment decreased macrophage and T helper 1/Th17 cell infiltration while promoting smooth muscle cell and collagen content. Mechanistically, IL-37 drove expansion of regulatory T cells and attenuated dendritic cell maturation in vivo and in vitro. The anti-atherosclerotic effects were dependent on interleukin 10 signalling, underscoring IL-37’s capacity to recalibrate vascular inflammation and to serve as a novel immunomodulatory intervention in atherosclerotic disease.

IL-37 Mediation of Inflammation and Immune Response publication trend

The graph below shows the total number of articles in il-37 mediation of inflammation and immune response across all publications each year (not limited to Nature Index journals).

Technical terms

Cytokine: A small secreted protein that mediates intercellular communication in immune responses.

Caspase-1: An intracellular protease that processes pro-inflammatory cytokines and IL-37 precursor into their active forms.

Inflammasome: A multiprotein complex that activates inflammatory caspases and promotes the maturation of interleukin-1 family cytokines.

Regulatory T cell (Treg): A subset of T lymphocytes that suppresses immune activation and maintains tolerance.

NF-κB: A transcription factor central to the induction of pro-inflammatory gene expression.

References

1. Current Understanding of IL-37 in Human Health and Disease. Frontiers in Immunology (2021).
2. Novel insights into IL-37: an anti-inflammatory cytokine with emerging roles in anti-cancer process. Frontiers in Immunology (2023).
3. Exogenous interleukin 37 ameliorates atherosclerosis via inducing the Treg response in ApoE-deficient mice. Scientific Reports (2017).