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单个 T1 细胞的可塑性和谱系决定由稳定的 T-bet 表达量决定。

Plasticity and lineage commitment of individual T1 cells are determined by stable T-bet expression quantities.

机构信息

Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Medical Department of Gastroenterology, Infectious Diseases and Rheumatology, 12203 Berlin, Germany.

German Rheumatism Research Center (DRFZ), a Leibniz Institute, Inflammatory Mechanisms, 10117 Berlin, Germany.

出版信息

Sci Adv. 2024 Jun 7;10(23):eadk2693. doi: 10.1126/sciadv.adk2693. Epub 2024 Jun 5.

DOI:10.1126/sciadv.adk2693
PMID:38838155
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11152138/
Abstract

T helper 1 (T1) cell identity is defined by the expression of the lineage-specifying transcription factor T-bet. Here, we examine the influence of T-bet expression heterogeneity on subset plasticity by leveraging cell sorting of distinct in vivo-differentiated T1 cells based on their quantitative expression of T-bet and interferon-γ. Heterogeneous T-bet expression states were regulated by virus-induced type I interferons and were stably maintained even after secondary viral infection. Exposed to alternative differentiation signals, the sorted subpopulations exhibited graded levels of plasticity, particularly toward the T2 lineage: T-bet quantities were inversely correlated with the ability to express the T2 lineage-specifying transcription factor GATA-3 and T2 cytokines. Reprogramed T1 cells acquired graded mixed T1 + T2 phenotypes with a hybrid epigenetic landscape. Continuous presence of T-bet in differentiated T1 cells was essential to ensure T1 cell stability. Thus, innate cytokine signals regulate T1 cell plasticity via an individual cell-intrinsic rheostat to enable T cell subset adaptation to subsequent challenges.

摘要

辅助性 T 细胞 1（T1）细胞的特征由谱系特异性转录因子 T 细胞因子结合蛋白（T-bet）的表达来定义。在这里，我们通过基于体内分化的 T1 细胞的 T-bet 和干扰素-γ的定量表达对其进行细胞分选，来研究 T-bet 表达异质性对亚群可塑性的影响。T-bet 的异质表达状态受病毒诱导的 I 型干扰素的调节，即使在二次病毒感染后也能稳定维持。暴露于替代分化信号下，分选的亚群表现出不同程度的可塑性，特别是向 T2 谱系：T-bet 量与表达 T2 谱系特异性转录因子 GATA-3 和 T2 细胞因子的能力呈反比。重新编程的 T1 细胞获得了具有混合表观遗传景观的分级混合 T1+T2 表型。分化的 T1 细胞中连续存在 T-bet 对于确保 T1 细胞的稳定性是必需的。因此，先天细胞因子信号通过个体细胞内变阻器来调节 T1 细胞的可塑性，从而使 T 细胞亚群能够适应随后的挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be4f/11152138/b8b0a16b2831/sciadv.adk2693-f8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be4f/11152138/b8b0a16b2831/sciadv.adk2693-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be4f/11152138/984cd2307fd4/sciadv.adk2693-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be4f/11152138/de325bb79068/sciadv.adk2693-f2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be4f/11152138/6c059c726116/sciadv.adk2693-f5.jpg
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