{"title":"Innateness transcriptome gradients characterize mouse T lymphocyte populations.","authors":"Gabriel Ascui, Viankail Cedillo-Castelan, Alba Mendis, Eleni Phung, Hsin-Yu Liu, Greet Verstichel, Shilpi Chandra, Mallory Paynich Murray, Cindy Luna, Hilde Cheroutre, Mitchell Kronenberg","doi":"10.1093/jimmun/vkae015","DOIUrl":null,"url":null,"abstract":"<p><p>A fundamental dichotomy in lymphocytes separates adaptive T and B lymphocytes, with clonally expressed antigen receptors, from innate lymphocytes, which carry out more rapid responses. Some T cell populations, however, are intermediates between these 2 poles, with the capacity to respond rapidly through T cell receptor activation or by cytokine stimulation. Here, using publicly available datasets, we constructed linear mixed models that not only define a gradient of innate gene expression in common for mouse innate-like T cells, but also are applicable to other mouse T lymphoid populations. A similar gradient could be identified for chromatin landscape based on ATAC-seq (assay for transposase-accessible chromatin using sequencing) data. The gradient included increased transcripts related to many traits of innate immune responses, with increased scores related to evidence for antigen experience. While including genes typical for T helper 1 (Th1) responses, the innateness gene program could be separated from Th1, Th2, and Th17 responses. Lymphocyte populations with higher innateness scores correlated with lower calcium-dependent T cell receptor-mediated cell activation, with some downstream signaling proteins dependent on calcium or affecting metabolism prephosphorylation. Therefore, as a group, different mouse innate-like T cell populations had related gene expression programs and activation pathways that are different from naive CD4 and CD8 T cells.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"214 2","pages":"223-237"},"PeriodicalIF":3.6000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878997/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/jimmun/vkae015","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
A fundamental dichotomy in lymphocytes separates adaptive T and B lymphocytes, with clonally expressed antigen receptors, from innate lymphocytes, which carry out more rapid responses. Some T cell populations, however, are intermediates between these 2 poles, with the capacity to respond rapidly through T cell receptor activation or by cytokine stimulation. Here, using publicly available datasets, we constructed linear mixed models that not only define a gradient of innate gene expression in common for mouse innate-like T cells, but also are applicable to other mouse T lymphoid populations. A similar gradient could be identified for chromatin landscape based on ATAC-seq (assay for transposase-accessible chromatin using sequencing) data. The gradient included increased transcripts related to many traits of innate immune responses, with increased scores related to evidence for antigen experience. While including genes typical for T helper 1 (Th1) responses, the innateness gene program could be separated from Th1, Th2, and Th17 responses. Lymphocyte populations with higher innateness scores correlated with lower calcium-dependent T cell receptor-mediated cell activation, with some downstream signaling proteins dependent on calcium or affecting metabolism prephosphorylation. Therefore, as a group, different mouse innate-like T cell populations had related gene expression programs and activation pathways that are different from naive CD4 and CD8 T cells.
期刊介绍:
The JI publishes novel, peer-reviewed findings in all areas of experimental immunology, including innate and adaptive immunity, inflammation, host defense, clinical immunology, autoimmunity and more. Special sections include Cutting Edge articles, Brief Reviews and Pillars of Immunology. The JI is published by The American Association of Immunologists (AAI)