The first functional characterization of ancient interleukin-15-like (IL-15L) reveals shared and distinct functions of the IL-2, -15 and -15L family cytokines

Yamaguchi, T.; Karger, A.; Keller, M.; Wangkahart, E.; Wang, T.; Secombes, C. J.; Kimoto, A.; Furihata, M.; Hashimoto, K.; Fischer, U.; Dijkstra, J. M.

doi:10.1101/644955

bioRxiv · 10.1101/644955

The first functional characterization of ancient interleukin-15-like (IL-15L) reveals shared and distinct functions of the IL-2, -15 and -15L family cytokines

Yamaguchi, T.·Karger, A.·Keller, M.·Wangkahart, E.·Wang, T.·Secombes, C. J.·Kimoto, A.·Furihata, M.·Hashimoto, K.·Fischer, U.·Dijkstra, J. M.

View original source ↗Export metadata ↓

Abstract

The ancient cytokine interleukin 15-like (IL-15L) was lost in humans and mice but not throughout mammals. This is the first study to describe IL-15L functions, namely in the fish rainbow trout. Fish have only one -chain receptor gene IL-15R, whereas in mammalian evolution this gene duplicated and evolved into IL-15R plus IL-2R. Trout IL-2, IL-15 and IL-15L all could bind IL-15R and were able to induce phosphorylation of transcription factor STAT5. Reminiscent of the mammalian situation, trout IL-15 was more dependent on \"in trans\" presentation by IL-15R than IL-2. However, whereas trout IL-15 could also function as a free cytokine as known for mammalian IL-15, trout IL-15L function showed a total dependency on in trans presentation by IL-15R. Trout lymphocytes from the mucosal tissues gill and intestine were sensitive to IL-15, but refractory to IL-2 and IL-15L, which is reminiscent of sensitivities to IL-15 in mammals. Distinguishing engagement of the IL-2R/IL-15R receptor chain may explain why IL-2 and IL-15 were selected in evolution as major growth factors for regulatory T cells and lymphocytes in mucosal tissues, respectively. Trout IL-15L efficiently induced expression of IL-4 and IL-13 homologues in CD4-CD8-IgM- splenocytes, and we speculate that the responsive cells within that population were type 2 innate lymphoid cells (ILC2). In contrast, trout IL-15 efficiently induced expression of interferon {gamma} and perforin in CD4-CD8-IgM- splenocytes, and we speculate that in this case the responsive cells were natural killer (NK) cells. In fish, in apparent absence of IL-25, IL-33 and TSLP, primitive IL-15L may have an important role early in the type 2 immunity cytokine cascade. Among trout thymocytes, only CD4-CD8- thymocytes were sensitive to IL-15L, and different than in mammals the CD4+CD8+ thymocytes were quite sensitive to IL-2. In addition, the present study provides (i) the first molecular evidence for inter-species cytokine with receptor chain interaction across fish-mammal borders, and (ii) suggestive evidence for a tendency of IL-2/15/15L cytokines to form homodimers as an ancient family trait. This is the first comprehensive study on IL-2/15/15L functions in fish and it provides important insights into the evolution of this cytokine family.

Explore related subjects

evolutionary biology Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Yamaguchi, T., Karger, A., Keller, M., Wangkahart, E., Wang, T., Secombes, C. J., Kimoto, A., Furihata, M., Hashimoto, K., Fischer, U., Dijkstra, J. M.. 2019-05-23. The first functional characterization of ancient interleukin-15-like (IL-15L) reveals shared and distinct functions of the IL-2, -15 and -15L family cytokines. https://doi.org/10.1101/644955

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Ocean current models predict spatial structure for coastal biodiversity

Genomic diversity provides the raw material through which all evolutionary processes occur. Accurately describing how environmental features affect patterns of diversity shows promise in predicting the resilience of populations and entire communities to dynamic environments and novel stressors. Identifying the contribution of purely neutral responses to environmental effects can be difficult, especially across large spatial ranges with many covarying environmental features. Using an individual-based model of larvae carried by ocean currents, we predict patterns of neutral genomic diversity in a passively dispersed coastal species, suggesting large geographic regions of relative homogeneity with ancestry determined by the nearest "upstream" population with limited larval input. The genomic identity that dominates each region sharply transitions at the next such interruption, generating hierarchical structure and violating assumptions of isolation-by-distance. We call these upstream populations "lineage source regions" (LSRs), and we find strong concordance between LSR model predictions and an empirical population genomic survey of a keystone salt marsh mussel (Geukensia demissa). We quantitatively validate model performance and goodness-of-fit, updating baseline predictions of genomic diversity patterns from the classic isolation-by-distance model to this LSR framework. This spatially explicit coastal ancestry model has potential for generalization across passive dispersing species.

evolutionary biology↗

bioRxiv2026

TaxaAudit: A statistical model of consensus in phylogenetics identifies non-monophyletic taxa

Interpreting variation in genes and traits across species requires understanding their evolutionary relationships. Taxonomic hierarchies provide a practical approximation of the tree of life, with the NCBI taxonomy linking this framework directly to public sequence data. Some named groups, however, are not evolutionary clades, and recognizing these exceptions requires knowledge scattered across the phylogenetics literature. Here we introduce TaxaAudit, a statistical model that identifies taxonomic groups whose monophyly is repeatedly contradicted by published phylogenies. The model accounts for background taxonomic conflict and the ability of each study's species sampling to expose non-monophyly. Applied to 5,865 molecular phylogenies from TimeTree, TaxaAudit flagged 516 NCBI taxa at family rank and below for significant recurrent contradiction of monophyly. Excluding these taxa's monophyly requirements improved the taxonomy's agreement with independent phylogenomic reference trees and phylogenies withheld from discovery. Flagged taxa were also 3.61 times as likely as matched controls to have their monophyly challenged in publications outside the discovery set. In tree-inference experiments, excluding these monophyly constraints improved agreement with reference phylogenies relative to enforcing the unmodified taxonomy. By identifying groups whose monophyly should not be assumed, TaxaAudit lets researchers draw on published phylogenetic knowledge without reviewing the specialist literature for every taxon. This supports broader use of the NCBI taxonomy as an evolutionary framework for biological comparisons.

evolutionary biology↗

bioRxiv2026

Shared landscape, divergent genomes: Comparative population genomics of co-occurring flora in an isolated Australian mountain range

Understanding how landscape heterogeneity shapes genomic variation is key to conserving biodiversity and evolutionary potential. Yet conservation genomics is typically conducted at the single species level, limiting our ability to identify shared genomic patterns or understand how co-occurring taxa differ in their response to common environmental gradients. We assessed spatial patterns of genomic variation and their associations with geographic and environmental features among populations of nine co-existing plant species with contrasting life-histories and ecological traits across Gariwerd, a threatened biodiversity hotspot in south-eastern Australia. All species exhibited weak overall genetic structure, although the magnitude and spatial distribution of differentiation varied among species. Despite this variation, broadly consistent spatial trends were apparent, with higher genomic divergence largely concentrated in central zones and higher genomic diversity localised in southern regions of the landscape. Significant associations between genetic differentiation and geographic distance were observed in three species, while another species showed associations with environmental distance. These findings demonstrate that coexisting species can show overlapping spatial patterns in genomic variation while differing markedly in their associations with geographic and environmental variation across the same landscape. This comparative approach provides a basis for spatial prioritisation and conservation planning, while highlighting the complex eco-evolutionary processes operating across heterogeneous landscapes.

evolutionary biology↗