Interleukin-1 Signaling in Immune Response

Interleukin-1 (IL-1) signalling is central to the initiation and regulation of innate and adaptive immunity. IL-1 exists as two agonistic isoforms, IL-1α and IL-1β, which engage the type I IL-1 receptor (IL-1R1) and recruit an accessory chain to form a signalling competent complex. This assembly nucleates adaptor proteins such as MyD88, IRAKs and TRAFs, driving activation of NF-κB and MAP kinase cascades and culminating in expression of proinflammatory mediators. A naturally occurring antagonist, IL-1Ra, competes for receptor binding without eliciting signal transduction, providing a critical brake on excessive inflammation. Dysregulation of IL-1 signalling underlies a spectrum of autoinflammatory and autoimmune conditions, and blockade of this pathway has yielded effective therapies for rheumatoid arthritis, cryopyrin-associated periodic syndromes and other disorders. Emerging research now focuses on characterising cell-type specific responses, mapping dynamic receptor interactions and developing selective modulators that fine-tune IL-1 activity while preserving host defence.

Research from Nature Portfolio

Recent studies have elucidated the structural dynamics of IL-1 receptor complex formation. High-resolution analyses revealed transient conformational states of IL-1R1 and its accessory protein that govern recruitment of MyD88 and signal fidelity. Single-cell transcriptomic profiling of human macrophages exposed to IL-1β uncovered unexpected heterogeneity in cytokine expression programmes and feedback circuits that limit inflammatory escalation. In parallel, small-molecule modulators targeting key protein–protein interfaces within the receptor assembly have been shown to attenuate joint inflammation in preclinical arthritis models, demonstrating proof of principle for novel therapeutics that conserve basal immunity while restraining pathological IL-1 activity.

Interleukin-1 Signaling in Immune Response publication trend

The graph below shows the total number of articles in interleukin-1 signaling in immune response across all publications each year (not limited to Nature Index journals).

Technical terms

Cytokine: A soluble protein released by cells to coordinate immune and inflammatory responses.

Interleukin-1 receptor type I (IL-1R1): A cell-surface receptor that binds IL-1 and assembles with a co-receptor to initiate intracellular signalling.

Interleukin-1 receptor accessory protein (IL-1RAcP): The co-receptor subunit required for formation of the active IL-1 receptor signalling complex.

Single-cell RNA sequencing: A technique for profiling gene expression in individual cells, revealing diverse cellular responses.

Cryo-electron microscopy (cryo-EM): A method for imaging biological molecules at near-atomic resolution under cryogenic conditions.

References

1. Interleukin-1 (IL-1) receptor antagonist binds to the 80-kDa IL-1 receptor but does not initiate IL-1 signal transduction. Journal of Biological Chemistry (1991).
2. Mapping Receptor Binding Sites in Interleukin (IL)-1 Receptor Antagonist and IL-1β by Site-directed Mutagenesis IDENTIFICATION OF A SINGLE SITE IN IL-1ra AND TWO SITES IN IL-1β*. Journal of Biological Chemistry (1995).
3. Expression and characterization of recombinant IL-1Ra in Aspergillus oryzae as a system. BMC Biotechnology (2023).