奥地利科学院分子医学研究中心Christoph Bock和Matthias Farlik共同合作，近期取得重要工作进展。他们研究提出，JAK-STAT信号在T细胞和巨噬细胞中维持稳态。相关研究成果2024年4月24日在线发表于《自然—免疫学》杂志上。

据介绍，免疫细胞需要在一生中保持持续的警觉状态。然而，人们对控制这种被称为"稳态"的微妙平衡调节过程知之甚少。

研究人员证明了JAK-STAT信号传导，除了在免疫反应中发挥功能外，还是免疫细胞稳态的主要调节因子。研究人员分析了12个小鼠模型中JAK-STAT介导的转录和染色质可及性，包括所有STAT转录因子和TYK2激酶的敲除。在未受干扰小鼠的CD8⁺ T细胞和巨噬细胞中检测到基线JAK-STAT信号，但在敲除和被剥夺正常组织环境的未受刺激的免疫细胞中被消除。研究人员观察到不同的基因调控程序，包括独立于STAT1的STAT2和IRF9的作用。

总之，对JAK-STAT突变体和野生型小鼠的大规模数据集和综合分析揭示了JAK-STAT信号在未刺激的免疫细胞中的关键作用，它有助于稳定的表观遗传和转录状态，并帮助这些细胞为对免疫刺激的快速反应做好准备。

附：英文原文

Title: JAK-STAT signaling maintains homeostasis in T cells and macrophages

Author: Fortelny, Nikolaus, Farlik, Matthias, Fife, Victoria, Gorki, Anna-Dorothea, Lassnig, Caroline, Maurer, Barbara, Meissl, Katrin, Dolezal, Marlies, Boccuni, Laura, Ravi Sundar Jose Geetha, Aarathy, Akagha, Mojoyinola Joanna, Karjalainen, Anzhelika, Shoebridge, Stephen, Farhat, Asma, Mann, Ulrike, Jain, Rohit, Tikoo, Shweta, Zila, Nina, Esser-Skala, Wolfgang, Krausgruber, Thomas, Sitnik, Katarzyna, Penz, Thomas, Hladik, Anastasiya, Suske, Tobias, Zahalka, Sophie, Senekowitsch, Martin, Barreca, Daniele, Halbritter, Florian, Macho-Maschler, Sabine, Weninger, Wolfgang, Neubauer, Heidi A., Moriggl, Richard, Knapp, Sylvia, Sexl, Veronika, Strobl, Birgit, Decker, Thomas, Mller, Mathias, Bock, Christoph

Issue&Volume: 2024-04-24

Abstract: Immune cells need to sustain a state of constant alertness over a lifetime. Yet, little is known about the regulatory processes that control the fluent and fragile balance that is called homeostasis. Here we demonstrate that JAK-STAT signaling, beyond its role in immune responses, is a major regulator of immune cell homeostasis. We investigated JAK-STAT-mediated transcription and chromatin accessibility across 12 mouse models, including knockouts of all STAT transcription factors and of the TYK2 kinase. Baseline JAK-STAT signaling was detected in CD8+ T cells and macrophages of unperturbed mice—but abrogated in the knockouts and in unstimulated immune cells deprived of their normal tissue context. We observed diverse gene-regulatory programs, including effects of STAT2 and IRF9 that were independent of STAT1. In summary, our large-scale dataset and integrative analysis of JAK-STAT mutant and wild-type mice uncovered a crucial role of JAK-STAT signaling in unstimulated immune cells, where it contributes to a poised epigenetic and transcriptional state and helps prepare these cells for rapid response to immune stimuli. Bock and colleagues perform integrative analysis of JAK-STAT mutant mice and find JAK-STAT signaling regulates CD8+ T cell and macrophage homeostasis by contributing to a poised epigenetic and transcription-regulatory state, preparing cells to rapidly respond to stimuli.

DOI: 10.1038/s41590-024-01804-1

Source: https://www.nature.com/articles/s41590-024-01804-1