ArticlePLoS pathogens2022
IL-2-mTORC1 signaling coordinates the STAT1/T-bet axis to ensure Th1 cell differentiation and anti-bacterial immune response in fish.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 42 citations in OpenAlex.
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- Legumain Restrains Granuloma Formation by Inhibiting mTORC1/STAT1-Mediated M1 Macrophage Polarization in Sarcoidosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Gut T cell-microbiota crosstalk orchestrates antibacterial immunity and mucosal homeostasis in teleost.Microbiome · 2026Article
- Endometriosis immune microenvironment timing shifts: from immune escape to immune exhaustion.Cell death discovery · 2026Review
- CTRP9 engages AdipoR1 and promotes T cell glycolysis and immunity.EMBO reports · 2025Article
- Dendritic Cells: Origin, Classification, Development, Biological Functions, and Therapeutic Potential.MedComm · 2025Review
- Single-Cell Transcriptome Profiling Reveals Conserved IFNγ-IL8 Signaling-Induced Antibacterial Neutrophil States during Bacterial Infection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cold-blooded vertebrates evolved regulatory B cells to participate in inflammatory diseases.Cell communication and signaling : CCS · 2025Article
- Dual phosphorylation of glycogen synthase kinase 3β differentially integrates metabolic programs to determine T cell immunity across vertebrates.Cellular and molecular life sciences : CMLS · 2025Article
- Advances and Challenges inVaccines · 2025Review
- Glutamine metabolism and ammonia death: targeted modulation for enhanced cancer immunotherapy.Frontiers in immunology · 2025Review
- Lactylation and antitumor immunity.Frontiers in immunology · 2025Review
- Single-cell transcriptomics unveils leukocyte heterogeneity in the gills ofFrontiers in immunology · 2025Article
- Identification of hub genes in congenital hypothyroidism and construction of the associated immune regulatory network.Frontiers in immunology · 2025Article
- Cold-blooded vertebrate utilizes behavioral fever to alleviate T cell apoptosis and optimize antimicrobial immunity.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Full T-cell activation and function in teleosts require collaboration of first and co-stimulatory signals.Zoological research · 2024Article
- Efficacy, safety, and serum cytokine modulation by olopatadine hydrochloride and desloratadine citrate disodium combination therapy in urticaria.American journal of translational research · 2024Article
- Dietary restriction to optimize T cell immunity is an ancient survival strategy conserved in vertebrate evolution.Cellular and molecular life sciences : CMLS · 2023Article
- Post-translational modifications and immune responses in liver cancer.Frontiers in immunology · 2023Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Utilization of specialized Th1 cells to resist intracellular pathogenic infection represents an important innovation of adaptive immunity. Although transcriptional evidence indicates the potential presence of Th1-like cells in some fish species, the existence of CD3+CD4+IFN-γ+ T cells, their detailed functions, and the mechanism determining their differentiation in these early vertebrates remain unclear. In the present study, we identified a population of CD3+CD4-1+IFN-γ+ (Th1) cells in Nile tilapia upon T-cell activation in vitro or Edwardsiella piscicida infection in vivo. By depleting CD4-1+ T cells or blocking IFN-γ, Th1 cells and their produced IFN-γ were found to be essential for tilapia to activate macrophages and resist the E. piscicida infection. Mechanistically, activated T cells of tilapia produce IL-2, which enhances the STAT5 and mTORC1 signaling that in turn trigger the STAT1/T-bet axis-controlled IFN-γ transcription and Th1 cell development. Additionally, mTORC1 regulates the differentiation of these cells by promoting the proliferation of CD3+CD4-1+ T cells. Moreover, IFN-γ binds to its receptors IFNγR1 and IFNγR2 and further initiates a STAT1/T-bet axis-mediated positive feedback loop to stabilize the Th1 cell polarization in tilapia. These findings demonstrate that, prior to the emergence of tetrapods, the bony fish Nile tilapia had already evolved Th1 cells to fight intracellular bacterial infection, and support the notion that IL-2-mTORC1 signaling coordinates the STAT1/T-bet axis to determine Th1 cell fate, which is an ancient mechanism that has been programmed early during vertebrate evolution. Our study is expected to provide novel perspectives into the evolution of adaptive immunity.
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