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International nomenclature guidelines for the IL-1 family of cytokines and receptors

Nature Immunology volume 25, pages 581–582 (2024)Cite this article

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Over the past 40 years, the IL-1 family has grown to include 22 members, with 11 cytokines and 11 receptors. After the initial description of the first IL-1 family members, confusion has grown about the nomenclature of IL-1 cytokines and receptors, which was last updated in 20101. This confusion arose from different names for the proteins identified by function. Several names for the same cytokine or receptor are particularly problematic for the IL-1 family. For example, two different receptors have been named ‘IL-1R9’ — the receptors encoded by IL1RAPL1 and by IL1RAPL2. Similarly, ‘IL-1R10’ is a name used for the gene products of both IL1RAPL1 and IL1RAPL2. Only a few of the companies selling antibodies to IL-1R9 specify which receptor their antibodies recognize. Because the IL-1 family factors represent a key signaling cascade in inflammation, clear and universally adopted guidelines for IL-1 nomenclature are needed. Here, we propose a nomenclature for both receptors and cytokines in the IL-1 family, based on common accepted practice and previous proposals2,3. We hope that this updated classification will help researchers and companies commit to adopting universal IL-1 family nomenclature guidelines.

The 11 members of the IL-1 family of receptors includes 10 structurally related receptors and the IL-18 binding protein (IL-18BP)2,4. These receptors include five ligand-binding receptors, two accessory chains, three receptors with inhibitory properties, and one orphan receptor (Table 1). In mammals, the IL-1 family receptors are characterized by an extracellular portion that contains three immunoglobulin domains (except IL-1R8 that has only one). Furthermore, apart from IL-1R2, each receptor possesses an intracellular portion that includes a Toll/interleukin-1 receptor (TIR) domain.

Table 1 IL-1 family receptors
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References

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Acknowledgements

The authors wish to thank all the colleagues in the field of the IL-1 family for their invaluable contributions, and regret the inability to refer to all the important studies that have helped shed light on notable properties of this family.

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Author notes

  1. These authors contributed equally: Joseph M. Gaballa, Jesper Falkesgaard Højen.

  2. These authors jointly supervised this work: Charles A. Dinarello, Diana Boraschi.

Authors and Affiliations

  1. Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Joseph M. Gaballa, Jesper Falkesgaard Højen, Dennis M. De Graaf, Jesus Amo-Aparicio, Carlo Marchetti, Alberto Dinarello, Suzhao Li, Michaele Francesco Corbisiero, Isak W. Tengesdal, Tania Azam, William S. Webber III, Karl A. Pankratz, Makenna J. May & Charles A. Dinarello

  2. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

    Jesper Falkesgaard Højen

  3. Institute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany

    Dennis M. De Graaf

  4. Vita-Salute San Raffaele University, Milan, Italy

    Giulio Cavalli

  5. Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), University of Copenhagen, Copenhagen, Denmark

    Alberto Dinarello

  6. Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, Aurora, CO, USA

    Jasmina S. Redzic & Elan Z. Eisenmesser

  7. Case Western Reserve University, Cleveland, OH, USA

    Fabio Cominelli

  8. College of Veterinary Medicine, Konkuk University, Seoul, Korea

    Soohyun Kim

  9. Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Science (CAS), and China-Italy Joint Laboratory of Pharmacobiotechnology for Medical Immunomodulation, Shenzhen, China

    Diana Boraschi

  10. National Research Council, Napoli, Italy

    Diana Boraschi

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  1. Joseph M. Gaballa
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  19. Charles A. Dinarello
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Corresponding author

Correspondence to Joseph M. Gaballa.

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Competing interests

G.C. is an employee of, and holds stocks in, Novartis. All other authors declare no competing interests.

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Gaballa, J.M., Højen, J.F., De Graaf, D.M. et al. International nomenclature guidelines for the IL-1 family of cytokines and receptors. Nat Immunol 25, 581–582 (2024). https://doi.org/10.1038/s41590-024-01777-1

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