학술논문
JAK-STAT signaling maintains homeostasis in T cells and macrophages
Document Type
Article
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; Müller, Mathias; Bock, Christoph
Source
Nature Immunology; 20240101, Issue: Preprints p1-13, 13p
Subject
Language
ISSN
15292908; 15292916
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.