Identification and bioactivity of a programmed death-ligand 1 homologue in large yellow croaker (Larimichthys crocea).
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| Main Authors: | , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
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Fish & shellfish immunology
2025
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| _version_ | 1868266174385487872 |
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| author | Li, Qiuhua Chen, Yuhong Wang, Meiyan Li, Chenhao Ao, Jingqun Li, Shengkang Chen, Xinhua |
| author_facet | Li, Qiuhua Chen, Yuhong Wang, Meiyan Li, Chenhao Ao, Jingqun Li, Shengkang Chen, Xinhua Li, Qiuhua Chen, Yuhong Wang, Meiyan Li, Chenhao Ao, Jingqun Li, Shengkang Chen, Xinhua |
| collection | PubMed - marine biology |
| contents | Identification and bioactivity of a programmed death-ligand 1 homologue in large yellow croaker (Larimichthys crocea). Li, Qiuhua Chen, Yuhong Wang, Meiyan Li, Chenhao Ao, Jingqun Li, Shengkang Chen, Xinhua Animals Perciformes B7-H1 Antigen Fish Proteins Fish Diseases Ciliophora Infections Phylogeny Amino Acid Sequence Sequence Alignment Gene Expression Regulation Immunity, Innate Ciliophora Gene Expression Profiling As a pivotal checkpoint molecule in immune system, programmed death-ligand 1 (PD-L1) orchestrates T cell immunity by suppressing T cell proliferation/activation, promoting apoptosis/anergy/exhaustion, and inducing regulatory T cell differentiation. Although teleosts possess a PD-L1 homologue capable of executing analogous functions, its immunological mechanisms remain largely uncharacterized. Here, we characterized a PD-L1 homologue (LcPD-L1) in a commercially significant species, Larimichthys crocea. Structural analysis reveals that it possesses conserved extracellular IgV-like and IgC-like domains with four critical cysteine residues. Phylogenetic analysis also confirmed its evolutionary relationship with vertebrate PD-L1. Under physiological conditions, LcPD-L1 exhibited constitutive expression across various tissues, particularly with high expression in mucosal tissues such as gills and skin. Besides that, pathogen challenge with Cryptocaryon irritans triggered significant up-regulation of LcPD-L1 in these tissues, suggesting it may play an important regulatory role in immune response elicited by C. irritans infection. In vitro assays revealed that recombinant LcPD-L1 protein (rLcPD-L1) inhibited T cell proliferation, decreased the expression levels of T cell activation markers (IL-2, LCK, and CD40L), and up-regulated the expression of the immune inhibitory cytokine (IL-10). Furthermore, rLcPD-L1 significantly inhibited the phosphorylation levels of MEK1/2 and ERK1/2 in the MAPK/ERK signaling pathway, as well as mTOR and 4E-BP1 in the mTOR signaling pathway, both of which are essential for T cell activation. Collectively, our findings imply that PD-L1 may inhibit T cell responses via the MAPK/ERK and mTOR pathways in teleosts, thus playing a role in pathogen elicited immune response. |
| format | Artículo científico |
| id | pubmed_40712760 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Fish & shellfish immunology |
| record_format | pubmed |
| spellingShingle | Identification and bioactivity of a programmed death-ligand 1 homologue in large yellow croaker (Larimichthys crocea). Li, Qiuhua Chen, Yuhong Wang, Meiyan Li, Chenhao Ao, Jingqun Li, Shengkang Chen, Xinhua Animals Perciformes B7-H1 Antigen Fish Proteins Fish Diseases Ciliophora Infections Phylogeny Amino Acid Sequence Sequence Alignment Gene Expression Regulation Immunity, Innate Ciliophora Gene Expression Profiling Identification and bioactivity of a programmed death-ligand 1 homologue in large yellow croaker (Larimichthys crocea). Li, Qiuhua Chen, Yuhong Wang, Meiyan Li, Chenhao Ao, Jingqun Li, Shengkang Chen, Xinhua Animals Perciformes B7-H1 Antigen Fish Proteins Fish Diseases Ciliophora Infections Phylogeny Amino Acid Sequence Sequence Alignment Gene Expression Regulation Immunity, Innate Ciliophora Gene Expression Profiling As a pivotal checkpoint molecule in immune system, programmed death-ligand 1 (PD-L1) orchestrates T cell immunity by suppressing T cell proliferation/activation, promoting apoptosis/anergy/exhaustion, and inducing regulatory T cell differentiation. Although teleosts possess a PD-L1 homologue capable of executing analogous functions, its immunological mechanisms remain largely uncharacterized. Here, we characterized a PD-L1 homologue (LcPD-L1) in a commercially significant species, Larimichthys crocea. Structural analysis reveals that it possesses conserved extracellular IgV-like and IgC-like domains with four critical cysteine residues. Phylogenetic analysis also confirmed its evolutionary relationship with vertebrate PD-L1. Under physiological conditions, LcPD-L1 exhibited constitutive expression across various tissues, particularly with high expression in mucosal tissues such as gills and skin. Besides that, pathogen challenge with Cryptocaryon irritans triggered significant up-regulation of LcPD-L1 in these tissues, suggesting it may play an important regulatory role in immune response elicited by C. irritans infection. In vitro assays revealed that recombinant LcPD-L1 protein (rLcPD-L1) inhibited T cell proliferation, decreased the expression levels of T cell activation markers (IL-2, LCK, and CD40L), and up-regulated the expression of the immune inhibitory cytokine (IL-10). Furthermore, rLcPD-L1 significantly inhibited the phosphorylation levels of MEK1/2 and ERK1/2 in the MAPK/ERK signaling pathway, as well as mTOR and 4E-BP1 in the mTOR signaling pathway, both of which are essential for T cell activation. Collectively, our findings imply that PD-L1 may inhibit T cell responses via the MAPK/ERK and mTOR pathways in teleosts, thus playing a role in pathogen elicited immune response. |
| title | Identification and bioactivity of a programmed death-ligand 1 homologue in large yellow croaker (Larimichthys crocea). |
| topic | Animals Perciformes B7-H1 Antigen Fish Proteins Fish Diseases Ciliophora Infections Phylogeny Amino Acid Sequence Sequence Alignment Gene Expression Regulation Immunity, Innate Ciliophora Gene Expression Profiling |
| url | https://pubmed.ncbi.nlm.nih.gov/40712760/ |