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Peer-reviewedCC BY-NC-ND 4.0Nature Ecology & Evolution

An ancient evolutionary origin for IL-1 cytokines

  • Francisco Fontenla-Iglesias1,2
  • Tse-Mao Lin3
  • Amelia G. Williams4
  • Sabyasachi Das1,2
  • Chia-Yen Lee3
  • Jonathan P. Rast1,2
  • Max D. Cooper1,2
  • Katherine M. Buckley4
  • Sebastian D. Fugmann3,5,6,7
7 affiliations
  1. 1Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA USA
  2. 2Emory Vaccine Center, Emory University, Atlanta, GA USA
  3. 3Graduate Institute of Biomedical Sciences, Chang Gung University, Tao-Yuan City, Taiwan
  4. 4Department of Biological Sciences, Auburn University, Auburn, AL USA
  5. 5Department of Biomedical Sciences, Chang Gung University, Tao-Yuan City, Taiwan
  6. 6Department of Nephrology, Chang Gung Memorial Hospital, Linkou, Taiwan
  7. 7Center for Molecular and Clinical Immunology, Chang Gung University, Tao-Yuan City, Taiwan
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Abstract

Inflammation is widely considered a hallmark of animal immune responses. In mammals, this process is mediated in part by pro-inflammatory cytokines of the interleukin 1 (IL-1) superfamily, which establish and support microenvironments that regulate immune cell activity. However, the evolutionary origins of IL-1 cytokines remain elusive, as homologous proteins have been difficult to confidently identify outside vertebrates using sequence-based approaches. Although IL-1 family members have been described in all vertebrate lineages, including cartilaginous and jawless fishes, their distribution and evolutionary relationships beyond these groups remain unclear. Here we applied protein structure prediction algorithms to identify genes encoding a previously unrecognized family of IL-1 proteins (termed ‘IL-1anc’ to reflect their ancestral evolutionary origin) with homologues throughout Eumetazoa. Here, using Petromyzon marinus (sea lamprey) and Strongylocentrotus purpuratus (purple sea urchin) as model systems, we demonstrate that IL-1anc proteins share key features with mammalian IL-1α/IL-1β, including expression patterns, subcellular localization and post-translational processing. Together with previous evidence identifying other IL-1 axis components in invertebrates, our data support a model in which the IL-1 superfamily and associated circuitry represent a foundational module of animal immunity that far predates the jawed vertebrates.

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Cite

BibTeXRIS
BibTeX
@article{fontenlaiglesias2026ancient,
  title = {{An ancient evolutionary origin for IL-1 cytokines}},
  author = {Francisco Fontenla-Iglesias and Tse-Mao Lin and Amelia G. Williams and Sabyasachi Das and Chia-Yen Lee and Jonathan P. Rast and Max D. Cooper and Katherine M. Buckley and Sebastian D. Fugmann},
  journal = {Nature Ecology \& Evolution},
  year = {2026},
  month = sep,
  doi = {10.1038/s41559-026-03191-2},
  url = {https://doi.org/10.1038/s41559-026-03191-2},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - An ancient evolutionary origin for IL-1 cytokines
AU  - Francisco Fontenla-Iglesias
AU  - Tse-Mao Lin
AU  - Amelia G. Williams
AU  - Sabyasachi Das
AU  - Chia-Yen Lee
AU  - Jonathan P. Rast
AU  - Max D. Cooper
AU  - Katherine M. Buckley
AU  - Sebastian D. Fugmann
PY  - 2026
DA  - 2026/09/30
JO  - Nature Ecology & Evolution
DO  - 10.1038/s41559-026-03191-2
UR  - https://doi.org/10.1038/s41559-026-03191-2
AB  - Inflammation is widely considered a hallmark of animal immune responses. In mammals, this process is mediated in part by pro-inflammatory cytokines of the interleukin 1 (IL-1) superfamily, which establish and support microenvironments that regulate immune cell activity. However, the evolutionary origins of IL-1 cytokines remain elusive, as homologous proteins have been difficult to confidently identify outside vertebrates using sequence-based approaches. Although IL-1 family members have been described in all vertebrate lineages, including cartilaginous and jawless fishes, their distribution and evolutionary relationships beyond these groups remain unclear. Here we applied protein structure prediction algorithms to identify genes encoding a previously unrecognized family of IL-1 proteins (termed ‘IL-1anc’ to reflect their ancestral evolutionary origin) with homologues throughout Eumetazoa. Here, using Petromyzon marinus (sea lamprey) and Strongylocentrotus purpuratus (purple sea urchin) as model systems, we demonstrate that IL-1anc proteins share key features with mammalian IL-1α/IL-1β, including expression patterns, subcellular localization and post-translational processing. Together with previous evidence identifying other IL-1 axis components in invertebrates, our data support a model in which the IL-1 superfamily and associated circuitry represent a foundational module of animal immunity that far predates the jawed vertebrates.
SN  - 2397-334X
ER  -