Ascui Gabriel, Cedillo-Castelan Viankail, Mendis Alba, Phung Eleni, Liu Hsin-Yu, Verstichel Greet, Chandra Shilpi, Murray Mallory Paynich, Luna Cindy, Cheroutre Hilde, Kronenberg Mitchell
La Jolla Institute for Immunology, La Jolla, CA, United States.
Department of Molecular Biology, University of California San Diego, La Jolla, CA, United States.
J Immunol. 2025 Feb 1;214(2):223-237. doi: 10.1093/jimmun/vkae015.
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.
淋巴细胞的一个基本二分法将具有克隆表达抗原受体的适应性T淋巴细胞和B淋巴细胞与进行更快反应的先天性淋巴细胞区分开来。然而，一些T细胞群体处于这两个极端之间，能够通过T细胞受体激活或细胞因子刺激快速做出反应。在这里，我们使用公开可用的数据集构建了线性混合模型，该模型不仅定义了小鼠先天性样T细胞共有的先天性基因表达梯度，而且适用于其他小鼠T淋巴细胞群体。基于ATAC-seq（使用测序的转座酶可及染色质分析）数据，可以识别出类似的染色质景观梯度。该梯度包括与许多先天性免疫反应特征相关的转录本增加，以及与抗原经历证据相关的得分增加。虽然包括典型的辅助性T细胞1（Th1）反应相关基因，但先天性基因程序可以与Th1、Th2和Th17反应区分开来。先天性得分较高 的淋巴细胞群体与较低的钙依赖性T细胞受体介导的细胞激活相关，一些下游信号蛋白依赖于钙或影响代谢预磷酸化。因此，作为一个群体，不同的小鼠先天性样T细胞群体具有与幼稚CD4和CD8 T细胞不同的相关基因表达程序和激活途径。
