Biology subjects

Lamas, J.

Publications and source records attributed to Lamas, J..

3 recordsLinked to original sources

bioRxiv2026

Ancient IL-6-STAT5 signaling orchestrates inflammation in jawless vertebrates

Interleukin-6 (IL-6) is a central regulator of vertebrate immunity, yet its existence in jawless vertebrates has remained obscure because of extreme sequence divergence. The extant jawless vertebrates (lampreys and hagfish), which deploy variable lymphocyte receptors (VLRs) instead of immunoglobulins and T cell receptors, provide a unique window into the earliest interface between cytokines and adaptive immunity. Here, we identify IL-6-like genes in jawless vertebrates by combining computational structural comparisons, phylogenetic reconstruction, and conserved local and long-range synteny analyses. The encoded proteins adopt the canonical four-helix bundle characteristic of immune-related IL-6 family cytokines and align topologically with mammalian IL-6. In sea lamprey, three IL-6 paralogs show distinct leukocyte and tissue expression patterns and are differentially induced by pathogen-associated molecular patterns and skin injury, indicating early functional diversification of IL-6-mediated inflammatory responses. Stimulation of myeloid peritoneal leukocytes with recombinant lamprey IL-6 induces STAT5 phosphorylation and rapid upregulation of SOCS1/3 genes, consistent with an IL-6/STAT5/SOCS regulatory axis. These findings extend the repertoire of immune-related four-helix bundle cytokines to jawless vertebrates and indicate that IL-6-dependent inflammatory programs were already in place before the divergence of VLR-based and Ig/TCR-based adaptive immune systems in vertebrates.

immunology↗

bioRxiv2024

Multiomics uncovers the epigenomic and transcriptomic response to viral and bacterial stimulation in turbot

Uncovering the epigenomic regulation of immune responses is essential for a comprehensive understanding of host defence mechanisms, though remains poorly investigated in farmed fish. We report the first annotation of the innate immune regulatory response in the turbot genome (Scophthalmus maximus), integrating RNA-Seq with ATAC-Seq and ChIP-Seq (H3K4me3, H3K27ac and H3K27me3) data from head kidney (in vivo) and primary leukocyte cultures (in vitro) 24 hours post-stimulation with viral (poly I:C) and bacterial (inactive Vibrio anguillarum) mimics. Among the 8,797 differentially expressed genes (DEGs), we observed enrichment of transcriptional activation pathways in response to Vibrio and immune pathways - including interferon stimulated genes - for poly I:C. We identified notable differences in chromatin accessibility (20,617 in vitro, 59,892 in vivo) and H3K4me3-bound regions (11,454 in vitro, 10,275 in vivo) between stimulations and controls. Overlap of DEGs with promoters showing differential accessibility or histone mark binding revealed significant coupling of the transcriptome and chromatin state. DEGs with activation marks in their promoters were enriched for similar functions to the global DEG set, but not always, suggesting key regulatory genes being in poised state. Active promoters and putative enhancers were enriched in specific transcription factor binding motifs, many common to viral and bacterial responses. Finally, an in-depth analysis of immune response changes in chromatin state surrounding key DEGs encoding transcription factors was performed. This multi-omics investigation provides an improved understanding of the epigenomic basis for the turbot immune responses and provides novel functional genomic information, leverageable for disease resistance selective breeding.

genomics↗

bioRxiv2019

Evidence for the role of extrusomes in evading attack by the host immune system in a scuticociliate parasite

Like other ciliates, the scuticociliate parasite of turbot, Philasterides dicentrarchi, produces only a feeding or growing stage called a trophont during its life cycle. Exposure of the trophonts to immune serum extracted from the host and containing specific antibodies that induce agglutination / immobilization leads to the production of a mucoid capsule from which the trophonts later emerge. We investigated how these capsules are generated, observing that the mechanism was associated with the process of exocytosis involved in the release of a matrix material from the extrusomes. The extruded material contains mucin-like glycoproteins that are deposited on the surface of the cell and whose expression increases with time of exposure to the turbot antibodies, at both protein expression and gene expression levels. Stimulation of the trophonts with host immune serum also causes an increase in discharge of the intracellular storage compartments of calcium necessary for the exocytosis processes in the extrusomes. The results obtained suggest that P. dicentrarchi uses the extrusion mechanism to generate a physical barrier protecting the ciliate from attack by soluble factors of the host immune system. Data on the proteins involved and the potential development of molecules that interfere with this exocytic process could contribute to the development of glycosylated recombinant vaccines and drugs to improve the prevention and control of scuticociliatosis in turbot.

microbiology↗